On April 18, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that preclinical data from its collaboration with Heat Biologics, Inc (Press release, OncoSec Medical, APR 18, 2016, View Source [SID:1234510979]). ("Heat") focused on evaluating the combination of immunotherapy platforms were presented yesterday at the American Conference for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (www.aacr.org).

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In the poster entitled "In vivo intra-tumoral electroporation of gp96-Ig/Fc-OX40L stimulates CD8+ T cell cross-priming to tumor specific neoantigens" (Abstract #567), researchers concluded that combining Heat’s ComPACT vaccine with OncoSec’s intratumoral DNA electroporation delivery platform stimulated an expansion of neoantigen-specific CD8+ T cells, leading to a regression in both treated and untreated cancer lesions in two mouse studies (melanoma and colorectal cancer). OncoSec and Heat announced their collaboration last year to evaluate the preclinical efficacy of delivering Heat’s immunotherapy vaccines via OncoSec’s ImmunoPulse platform.

"We are excited by our collaboration with Heat and by these initial findings. The ability of the tumor’s microenvironment to evade immune recognition and remain non-immunogenic is a significant challenge, which we believe needs to be addressed when designing new immuno-therapies," said Robert H. Pierce, MD, OncoSec’s Chief Scientific Officer. "The initial feasibility data between our two platforms are encouraging and we are currently exploring the potential synergy between our platforms with both ComPACT and interleukin-12 expressing plasmids."

"In this first preclinical study demonstrating the feasibility of electroporating ComPACT DNA plasmids, we saw robust neoantigen T cell response and tumor regression in both treated and untreated tumors, indicating a systemic anti-tumor response that could be reflective of what we might see in metastatic lesions," said Taylor Schreiber, MD, PhD, Heat’s Chief Scientific Officer. "We believe that this approach is promising and that further studies are merited, especially as this combination approach has the potential to stimulate shared and private tumor antigens without introducing the complexities associated with personalized therapies."

Copies of the abstract are available and can be viewed online through the AACR (Free AACR Whitepaper) website at www.aacr.org. The poster is available in the Publications section of OncoSec’s website.

On April 18, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported results from two programs will be presented in oral sessions at the upcoming 19th Annual American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Meeting (Press release, Ziopharm, APR 18, 2016, View Source [SID:1234511002]). The first presentation highlights preclinical data from the Company’s novel viral gene therapy candidate for the controlled expression of IL-12 in combination with inhibition of programmed cell death protein 1 (PD-1) in a mouse model of glioma. The second presentation highlights preclinical data from the Company’s evolution of the Sleeping Beauty (SB) non-viral transposon-transposase system in a mouse model of leukemia. The ASGCT (Free ASGCT Whitepaper) meeting will take place May 4-7 at the Marriott Wardman Park Hotel in Washington, D.C.

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Title: Regulated Expression of IL-12 as Gene Therapy Concomitant with Blockade of PD-1 for Treatment of Glioma
Session Title: Cancer-Immunotherapy, Cancer Vaccines II
Date and Time: Friday, May 6, 2016 4:00 PM – 6:00 PM ET
Abstract Number: 509
Room: Washington 1-2
Summary: The utility of clinically-feasible immunotherapy in the investigational treatment of glioma may be improved through combination therapies that enhance cytotoxic immune-activation while concomitantly reducing immunosuppression. ZIOPHARM and Intrexon evaluated the combination of controlled local interleukin 12 (IL-12) administration using a virus (Ad-RTS-IL-12) activated by an oral ligand (veledimex) (Ad +V) and blockade of PD-1 using a checkpoint inhibitor:

Results demonstrated that survival of mice treated with Ad +V and anti-PD-1 therapy was superior to either treatment alone;
Combination showed 100% survival;
Because Ad-RTS-IL-12 and anti-PD-1 are clinically available, these data provide impetus for evaluating this combination immunotherapy in humans;
ZIOPHARM plans to initiate a combination study in 2016 and is currently in discussion with partners to provide anti PD-1 therapy.
"The use of PD-1 checkpoint inhibitors in solid tumors has yielded impressive clinical outcomes, yet these results have not yet translated to gliomas, due in part to the immunologic privilege of the central nervous system," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "By combining PD-1 inhibitors, which release a brake on the immune system, with the controlled tumor-directed release of IL-12, which steps on the immune system’s accelerator, we see significant anti-tumor activity. These data provide a strong rationale for studying Ad-RTS-IL-12 + veledimex in combination with anti-PD-1 in the clinic, a trial we look forward to initiating later this year."

Title: Next-Generation Non-Viral Gene Transfer to Redirect T-Cell Specificity
Session Title: Cancer-Immunotherapy, Cancer Vaccines I
Date and Time: Thursday, May 5, 2016 4:00 PM – 5:45 PM ET
Abstract Number: 278
Room: Washington 5-6
Summary: Non-viral gene transfer using the SB transposon/transposase system has been successfully tested in humans to express a chimeric antigen receptor (CAR) to redirect T-cell specificity to CD19. A next-generation SB system has been modified by MD Anderson Cancer Center researchers to improve the design of a CD19-specific CAR as well as reduce the time to manufacture:

Changing the "stalk" of the CAR improved the anti-tumor activity of SB-modified T cells;
These data support the use of new CAR in an ongoing clinical trial (IND#16474).
Decreasing the time the SB-modified T cells were in culture improved the anti-tumor effect;
These data provide support for ZIOPHARM’s efforts to address the challenges of cost and time of bioprocessing cell therapies;
"Targeting CD19 with CAR-modified T cells is an effective approach to treating CD19-expressing leukemias and lymphomas, as demonstrated by current clinical studies," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "Fundamental to advancing this approach, and any modified cell-based therapy, into a broadly deployed treatment option is a streamlined and simplified manufacturing process, with a reduction in the associated cost. These data demonstrate our ability to address these challenges by leveraging the less costly, non-viral Sleeping Beauty system and reducing cell culture time, all while improving the effectiveness of the CD19-specific CAR. We look forward to understanding how these next-generation ideas translate into outcomes in an ongoing Phase 1 study and future clinical studies."

On April 18, 2016 Seattle Genetics, Inc. (NASDAQ: SGEN) reported multiple data presentations that support several of the company’s antibody-drug conjugate (ADC) and immuno-oncology programs featured at the upcoming 107th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) being held April 16 through 20, 2016 in New Orleans, LA (Press release, Seattle Genetics, APR 18, 2016, View Source;p=RssLanding&cat=news&id=2157809 [SID:1234510980]). The presentations describe preclinical data with SGN-LIV1A and SEA-CD40, which are in ongoing clinical trials, and highlight two preclinical programs, a novel ADC for the treatment of multiple myeloma (SGN-CD352A) and a small molecule that enhances T-cell mediated antitumor activity (2-fluorofucose). Additional data highlight the growing body of knowledge regarding the ability of auristatin-based ADCs, including ADCETRIS (brentuximab vedotin), to initiate immunogenic cell death, supporting evaluation in combination with checkpoint inhibitors.

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"Our ADC expertise currently empowers a robust pipeline of more than a dozen clinical and preclinical programs," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "At AACR (Free AACR Whitepaper), we will be presenting preclinical data that demonstrate encouraging activity with SGN-LIV1A, an ADC in phase 1 clinical development for breast cancer, and the preclinical development of a novel ADC for multiple myeloma, SGN-CD352A, which uses our newest ADC technology. We will also highlight the progress we have made in the important field of immuno-oncology, demonstrating that auristatin-based ADCs may be particularly well suited for combination with checkpoint inhibitors and presenting exciting preclinical data for SEA-CD40 and a small molecule, 2-fluorofucose."

Multiple presentations are being featured at AACR (Free AACR Whitepaper) that highlight advances with Seattle Genetics’ proprietary ADC and empowered antibody pipeline and research programs. Abstracts can be found at www.aacr.org and include the following:

Preclinical data from a novel ADC candidate SGN-CD352A for multiple myeloma will be highlighted in a poster presentation on Monday, April 18, 2016 (Abstract #1195). SGN-CD352A utilizes Seattle Genetics’ newest ADC technology and is composed of an anti-CD352 antibody attached to a highly potent cytotoxic DNA-crosslinking agent called a pyrrolobenzodiazepine (PBD) dimer via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb).
SGN-LIV1A will be highlighted in a poster presentation on Tuesday, April 19, 2016 (Abstract #2966) focusing on the potential of combination use with standard of care chemotherapeutic agents, including doxorubicin, paclitaxel (Abraxane), carboplatin and various kinase inhibitors, for the treatment of breast cancer. SGN-LIV1A is in a phase 1 trial for the treatment of LIV-1-expressing metastatic breast cancer.
A preclinical analysis will highlight the novel small molecule, 2-fluorofucose (2FF) in a poster presentation on Tuesday, April 19, 2016 (Abstract #4005). 2FF blocks cellular incorporation of a sugar (fucose) and has been shown in preclinical studies to stimulate T-cell receptor signaling leading to enhanced activation of dendritic cells.
The path of SEA-CD40 from research to clinical development will be highlighted in a poster presentation on Wednesday, April 20, 2016 (Abstract #4994). SEA-CD40 is in an ongoing phase 1 trial for patients with advanced malignancies. SEA-CD40 is a novel immuno-oncology agent targeted to CD40 utilizing Seattle Genetics’ proprietary sugar-engineered antibody (SEA) technology to produce a non-fucosylated antibody.
Preclinical data evaluating brentuximab vedotin (ADCETRIS) immune activity will be presented in a poster presentation on Wednesday, April 20, 2016 (Abstract #4914). The preclinical data being presented demonstrate that brentuximab vedotin treated tumor cells may initiate an antitumor immune response and supports combination strategies with immuno-oncology regimens, such as the ongoing phase 1/2 clinical trials evaluating ADCETRIS and nivolumab (Opdivo) in relapsed Hodgkin and non-Hodgkin lymphoma.
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On Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) today presented data demonstrating enhanced anti-tumor efficacy and survival by combining anti-NKG2A with PD-1/PD-L1 pathway inhibitors in murine models at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans, Louisiana, USA (Press release, Innate Pharma, APR 18, 2016, View Source [SID:1234511005]).

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The NKG2A checkpoint receptor is expressed on a subset of NK cells. Similar to the PD-1 receptors, NKG2A can also be induced on tumor-infiltrating CD8 T cells. Therefore, PD-1 and NKG2A may both inhibit anti-tumor immune responses in situations where cancers express the ligands of both these checkpoint receptors. Conversely, anti-tumor immune responses might be enhanced by combined NKG2A and PD-1 pathway blockade.

Poster #2342 reports preclinical data based on an in vivo model of PD-L1 expressing solid tumors. In this model, treatment with either an antibody blocking PD-1 or NKG2A as single agents resulted in modest anti-tumor efficacy. The frequency of tumor-infiltrating NKG2A+ CD8 T cells was increased in anti-PD-1 resistant mice, suggesting that NKG2A is a pathway involved in adaptive PD-1 resistance. Treatment with combination of NKG2A and PD-1 checkpoint inhibitors resulted in significantly enhanced anti-tumor responses. Nearly twice as many mice achieved complete tumor cell regression compared to treatment with anti PD-1 alone.

Nicolai Wagtmann, CSO of Innate Pharma, said: "We are very excited by these data showing that the NKG2A pathway acts as a major mechanism of tumor escape in this model. Considering the high frequency of patients who respond inadequately to PD-1 pathway blockade, we are intrigued by the observations that NKG2A expression on CD8 T cells was increased in PD-1 resistant mice". He added: "These data and the striking efficacy of the combination treatment in this model provide strong support for the clinical trial that was just initiated, testing the combination of monalizumab, Innate’s first-in-class NKG2A checkpoint inhibitor, and durvalumab, AstraZeneca/Medimmune’s investigational PD-L1 checkpoint inhibitor".

On April 18, 2016 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported data on a research program to develop a CD73 checkpoint inhibitor antibody in oncology at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans, Louisiana, USA (Press release, Innate Pharma, APR 18, 2016, View Source [SID:1234511075]). This new anti-CD73 project complements Innate’s first-in-class anti-CD39 program strengthening the Company’s positioning in targeting the tumor microenvironment.

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CD73 and CD39 are two enzymes which play a major role in promoting immunosuppression through the pathway degrading adenosine triphosphate (ATP) into adenosine. CD73 is active on the last step of the degradation pathway, where it is the enzyme that actually degrades AMP* into adenosine.

Poster #2344 presented a panel of newly generated antibodies that block CD73 function. They all bind with high affinity and specificity to the CD73 enzyme, but to distinct epitopes and display different mechanisms of inhibition, including direct blocking of CD73 enzymatic activity or down-modulation of CD73 membrane expression. All antibodies strongly reduce AMP catabolism and efficiently reverse adenosine-mediated T cell suppression in vitro. The antibodies displaying the most interesting features were humanized and further evaluation of their activity is ongoing.

Nicolai Wagtmann, CSO of Innate Pharma, said: "This program adds to our innovative and diversified portfolio of checkpoint inhibitors. We are entering the very exciting and novel area of microenvironment checkpoint inhibition which complements other immuno-oncology approaches. Our anti-CD73 and anti-CD39 antibodies each have potential as single-agent therapeutics and for combination with other checkpoint blockers notably targeting T or NK cells".