On November 8, 2019 Checkpoint Therapeutics, Inc. (Checkpoint) (NASDAQ: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported that new pharmacokinetic and target occupancy modeling data for cosibelimab (formerly referred to as CK-301) are being presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting, taking place in National Harbor, MD (Press release, Checkpoint Therapeutics, NOV 8, 2019, View Source [SID1234550767]).

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The poster, entitled, "Semi-mechanistic PK and target-occupancy modeling to support dose justification for anti-PD-L1 clinical candidate CK-301 (TG-1501) in oncology patients," compares pharmacokinetic and tumor target occupancy data at steady state under various dosing regimens of cosibelimab to those of three marketed anti-PD-L1 monoclonal antibodies, atezolizumab, durvalumab and avelumab. The results demonstrate that cosibelimab dosed at 800 mg and 1200 mg once every two weeks or every three weeks is expected to achieve over 99% PD-L1 target occupancy throughout the dosing interval, which is comparable to atezolizumab and durvalumab, and higher than avelumab, at their approved doses. These data support the potential of cosibelimab’s once every two-week and every three-week dosing regimens to achieve and maintain the PD-L1 target occupancy required to restore T-cell function and an anti-tumor response.

These data follow the presentation of positive interim clinical results for cosibelimab at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 in September. Checkpoint is currently enrolling cutaneous squamous cell carcinoma patients in an expanded cohort of its ongoing Phase 1 clinical trial to support an initial Biologics License Application submission for cosibelimab. Additional monotherapy and combination Phase 3 clinical trials are planned to expand the potential market opportunity for cosibelimab to multiple non-small cell lung cancer indications.

A copy of the poster presentation is available on the Publications page of the Pipeline section of Checkpoint’s website, www.checkpointtx.com.

Additional information on the meeting can be found on the SITC (Free SITC Whitepaper) website, www.sitcancer.org.

About Cosibelimab
Cosibelimab (formerly referred to as CK-301) is a high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 (PD-L1) and blocks the PD-L1 interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors. PD-L1 is an immune-inhibitory checkpoint molecule expressed on epithelial and vascular endothelial cells, as well as by a number of immune cells, and is utilized by tumor cells as an immune escape mechanism. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies with a half-life that supports sustained >99% target tumor occupancy and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) for potential enhanced efficacy in certain tumor types.

On November 8, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported that new data from Cohort 2 of the ongoing Phase 2 lifileucel metastatic melanoma study (C-144-01) were presented Friday, Nov. 8, 2019, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, Maryland (Abstract P865) (Press release, Iovance Biotherapeutics, NOV 8, 2019, View Source [SID1234550799]).

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Highlights from the poster presentation include:

An objective response rate (ORR) of 35 percent as assessed by IRC as compared to 36 percent as assessed by investigator
Median DOR was not reached as assessed by either IRC (range: 1.6+ to 21.2+ months) or investigator (range: 2.2 to 21.2+ months) at 11.3 months median follow up. In addition, based on the most recent data cut from the study, median DOR was not reached as assessed by investigator at 12.8 months of median study follow-up.
An overall concordance rate of 89.4 percent between investigator assessment and IRC assessment (n=66)
"We are pleased to see continued evidence of durability with lifileucel therapy as patients are evaluated with longer term follow-up," commented Maria Fardis, Ph.D., MBA, president and chief executive officer of Iovance Biotherapeutics. "In addition, concordance between IRC assessment and investigator reported results is highly favorable in this metastatic disease setting as compared with the published literature. These results continue to show that lifileucel offers a potential therapeutic option for the metastatic melanoma patients enrolled in this study. We continue to enroll patients in the pivotal cohort of the study, Cohort 4, which is expected to serve as the basis for an expected Biologics License Application (BLA) submission for lifileucel in late 2020."

Cohort 2 in the ongoing C-144-01 study includes consecutively dosed post-PD-1 patients with Stage IIIC/IV unresectable melanoma who also have received BRAF/MEK therapy if clinically indicated. In this study, patients had experienced a mean of 3.3 lines of prior therapy including anti-PD1 blocking antibody, and the patients had a high baseline tumor burden. The adverse event profile of lifileucel treatment in the C-144-01 study continued to be consistent with the underlying advanced disease and the profile of the lymphodepletion and IL-2 regimens.

On November 8, 2019 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported that the Company presented data from the Toca 6 Phase 1b study of Toca 511 and Toca FC in patients with non-CNS tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, MD and will have two presentations related to brain cancer at the 24th Annual Meeting of the Society for Neuro-Oncology (SNO), to be held Nov. 20-24 in Phoenix (Press release, Tocagen, NOV 8, 2019, View Source [SID1234550838]).

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The SITC (Free SITC Whitepaper) poster titled, "Immunomodulation in peripheral blood and tumor following Toca 511 & Toca FC treatment in patients with solid tumors," was a summary of the results in the Toca 6 Phase 1b, single arm study of Toca 511 and Toca FC in advanced non-CNS solid tumors. The objectives of the study were to assess changes in immune activity of peripheral blood mononuclear cells (PBMCs) relative to baseline following treatment and to evaluate immune cell modulation in the tumor microenvironment from tumor biopsies taken at baseline compared to biopsies collected following treatment.

Data Summary

The Toca 6 Phase 1b, single arm study of Toca 511 and Toca FC in advanced non-CNS solid tumors demonstrated vector deposition, immune activity, a potential signal of clinical activity and a favorable safety profile.

Treatment was generally well tolerated, with predominantly Grade 1 and 2 treatment-related gastrointestinal adverse events. Most patients enrolled (81%) had metastatic colorectal cancer; the median lines of prior chemotherapies was four (1, 12).
Clinical activity was supported by observations of partial response and stable disease. The median overall survival was 9.6 months (95% CI 6.3, 16.4) in this heavily pre-treated population.
Toca 511 and Toca FC was associated with a T-cell mediated immune response in peripheral blood and metastatic tumor in some patients, consistent with the mechanism of action observed in preclinical models.
Peripheral blood T-cells shift from naïve to effector phenotypes indicating that T-cells are encountering their target antigens, potentially including proteins released by tumor cell killing.
Expansion of CD4+ memory T-cells after treatment is consistent with engagement of the adaptive immune system.
Increased post-treatment quantities of B-cells further suggests immune activation during the course of Toca 511 and Toca FC therapy.
Toca 511 and Toca FC led to a decrease of CD11b+ myeloid cells in five of six patients with evaluable colorectal metastasis. This immune fluorescence analysis suggests a decrease in the immunosuppressive myeloid cells, as seen in preclinical models, and potentially makes the tumor and the tumor microenvironment more conducive to immunologic modulation.
"Data from our poster at SITC (Free SITC Whitepaper) are encouraging and support the planned exploration of our Toca regimen in non-muscle invasive bladder cancer," said Marty Duvall, chief executive officer of Tocagen. "In addition, we look forward to presenting Toca 5 analyses at the upcoming SNO conference Toca 5 analyses including subgroups and molecular data in addition to details of the planned NRG Oncology trial in patients with newly diagnosed glioblastoma."

Details of the SNO presentations are as follows. Copies of the presentations will be available on Tocagen’s website following the presentations.

Presentation Type: Plenary Presentation (Abstract: LTBK-08)
Title: Toca 511 & Toca FC Versus Standard of Care in Patients With Recurrent High Grade Glioma
Presenter: Timothy Cloughesy, M.D., director of the University of California, Los Angeles, Neuro-Oncology Program
Date and Time: Friday, Nov. 22, 11:50 a.m. – 12:00 p.m. MST

Presentation Type: Poster Presentation (Abstract: RBTT-11)
Title: NRG Oncology NRG-BN006: A phase II/III randomized, open-label study of Toca 511 and Toca FC with standard of care compared to standard of care in patients with newly diagnosed glioblastoma
Presenter: Manmeet Ahluwalia, M.D., head of operations, Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic.
Date and Time: Saturday, Nov. 23, 5:00 p.m. – 7:00 p.m. MST

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 8, 2019 Neon Therapeutics, Inc. (Nasdaq: NTGN), a clinical-stage immuno-oncology company developing neoantigen-based therapeutics, reported updated data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, MD (Press release, Neon Therapeutics, NOV 8, 2019, View Source [SID1234550751]).

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"We are pleased to present these updates for both NEO-PV-01 and NEO-PTC-01, both of which demonstrate Neon’s continued leadership in advancing neoantigen-based science and drug development. We continue to believe that these personalized approaches to treating cancer represent significant potential to reshape the treatment landscape for solid tumors," said Richard Gaynor, M.D., Neon’s President of Research and Development.

NEO-PV-01: Updated Results from the NT-001 Clinical Trial

Neon reported updated results (August 2019 data cut) from the ongoing, multicenter Phase 1b clinical trial evaluating NEO-PV-01, Neon’s personal neoantigen vaccine candidate, in combination with OPDIVO (nivolumab) in patients with advanced or metastatic melanoma, smoking-associated non-small cell lung cancer (NSCLC) and bladder cancer. Across all three distinct tumor types, results demonstrated prolonged and consistent improvements in progression-free survival (PFS) and overall survival (OS) that compare favorably to that observed with checkpoint inhibitor monotherapy, based on historical benchmark data. Further, neoantigen-specific immune responses and epitope spread to RECON-predicted targets were associated with longer PFS and major pathological responses post-administration of NEO-PV-01 in melanoma patients were also associated with longer PFS. The safety data for NT-001 were consistent with the safety profile for OPDIVO monotherapy. These updated results come from 82 patients who received at least one dose of OPDIVO in the Phase 1b NT-001 trial. The NT-001 trial was initiated in November 2016 and completed enrollment in July 2018.

NT-001 Clinical Trial Results
August 2019 data cut; overall survival analysis includes previously censored patients from April 2019 data cut
Initiated OPDIVO: Patients that received at least one dose of OPDIVO (ITT set)
Initiated NEO-PV-01: Patients who received at least one dose of NEO-PV-01 (ITT subset)

1 Historical checkpoint inhibitor data for advanced or metastatic melanoma: Larkin, et al, JCO 2017; Schachter, et al, Lancet 2017; Wolchok, et al, NEJM 2017.
2 Historical checkpoint inhibitor data for advanced or metastatic non-small cell lung cancer: Borghaei, et al, Lancet 2015; Carbone, et al, NEJM 2017; Herbst, et al, Lancet 2016.
3 Historical checkpoint inhibitor data for advanced or metastatic bladder cancer: Balar, et al, Lancet 2017; Bellmunt, et al, NEJM 2017; Sharma, et al, Lancet 2016.

NEO-PTC-01: Advanced Process Development Supports Clinical Trial Application Filing in Europe by End of 2019

Neon continues to advance its preclinical and process development work for NEO-PTC-01, its personal neoantigen-targeted T cell therapy candidate consisting of multiple T cell populations targeting the most therapeutically relevant neoantigens from each patient’s tumor. NEO-PTC-01 leverages Neon’s RECON bioinformatics platform to individually select a set of neoantigen targets for each patient, and NEO-STIM, its proprietary process to directly prime, activate and expand neoantigen-targeting T cells ex vivo. Neon believes that this approach will allow NEO-PTC-01, a non-engineered T cell product that leverages peripheral blood mononuclear cells (PBMCs) as its starting material, to specifically target each patient’s individual tumor with T cells that can drive a robust and persistent anti-tumor response.

In the update presented today at SITC (Free SITC Whitepaper), Neon demonstrated that it can reproducibly generate a potent T cell product from PBMCs of melanoma patients, as well as at therapeutic scale using a healthy donor sample. This process development work showed that NEO-PTC-01 induced multiple CD8+ and CD4+ T cell responses from both the memory and naïve T cell compartments. The induced T cell responses were mutant-specific, showed a polyfunctional profile and had a central and effector memory phenotype. The induced T cell responses had cytotoxic capability, shown by the recognition of antigen-expressing tumor cell lines. Importantly, NEO-PTC-01 induced T cell cultures that directly recognized autologous tumor digest.

Neon is focusing the initial clinical development of NEO-PTC-01 in patients with solid tumors that are refractory to checkpoint inhibitors. Neon expects to file a clinical trial application, or CTA, in Europe by the end of 2019 to evaluate NEO-PTC-01 in the solid tumor setting.

Details for the NEO-PV-01 poster presentation are as follows:

Presentation Title: Disease-related Biomarkers are Associated with Extended Progression-Free Survival after Treatment with NEO-PV-01 in Combination with Anti-PD1 in Patients with Metastatic Cancers
Poster Hall Hours: Friday, November 8 from 7:00 a.m. – 8:00 P.M. ET
Poster Number: P437
Location: Gaylord National Convention Center

Details for the NEO-PTC-01 poster presentation are as follows:

Presentation Title: The Development of an Autologous Neoantigen-Specific T cell Product from Peripheral Blood, NEO-PTC-01, through the ex-vivo Induction Protocol, NEO-STIM
Poster Hall Hours: Friday, November 8 from 7:00 a.m. – 8:00 P.M. ET
Poster Number: P197
Location: Gaylord National Convention Center

The posters will also be made available at View Source

OPDIVO is a registered trademark of Bristol-Myers Squibb Company.

On November 8, 2019 eHealth, Inc. (NASDAQ: EHTH), a leading private online health insurance exchange, reported that its senior management will deliver presentations at the following upcoming investor conferences (Press release, eHealthInsurance, NOV 8, 2019, View Source [SID1234550768]):

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28th Annual Credit Suisse Healthcare Conference, on Tuesday, November 12, 2019 at 11:30 a.m. M.T. The conference is being held at The Phoenician Resort in Scottsdale, Arizona.
Stephens Nashville Investment Conference, on Thursday, November 14, 2019 at 1:00 p.m. C.T. The conference is being held at the Omni Nashville, Nashville, TN.
Interested investors can access the live audio webcast of the presentations at www.ehealthinsurance.com under Investor Relations. Please visit the website at least 15 minutes early to register, download, and install any necessary software. A replay of this event will be available on the company’s website shortly after the conclusion of the event and will remain available for 14 days.

eHealth will also hold one-on-one and small group meetings with institutional investors at the 10th Annual Craig-Hallum Alpha Select Conference, on Tuesday, November 12th, 2019. The conference is being held at Sheraton Times Square Hotel, New York, NY.