On November 10, 2017 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing treatments for autoimmune/inflammatory diseases and cancer, reported immuno-oncology preclinical data characterizing the functional activity of molecules Alpine successfully generated from its variant immunoglobulin domain (vIgD) platform (Press release, Alpine Immune Sciences, NOV 10, 2017, View Source [SID1234521920]). Several novel immuno-oncology molecules were functionally active via multiple mechanisms of action, including the demonstration of tumor suppression in an animal model. The findings will be presented on Friday, November 10, in a poster session titled "Immune Modulation, Cytokines, and Antibodies" [#P343] at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 32nd Annual Meeting in National Harbor, MD.

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"Our unique vIgD platform is capable of producing first-in-class immuno-oncology biologics with potentially unique mechanisms of action," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. "This promising data highlights the versatility of the platform, showing vIgDs may be implemented in multiple therapeutic formats and may be tailored to modulate multiple molecular pathways according to the desired therapeutic application."

Preclinical Study Design and Results

Alpine scientists used the vIgD directed evolution platform to engineer a number of vIgDs with unique binding profiles to proteins relevant to the immune synapse, including PD-1, PD-L1, CTLA-4, TIGIT, CD155, CD28, and/or ICOS. The poster describes the vIgD domains in multiple therapeutic formats, including tumor-localized Fc fusion proteins, multi-checkpoint inhibitors, and vIgDs fused with tumor-specific monoclonal antibodies (V-mAbs). Various in vitro and in vivo tests characterized the functional activity of these potentially novel therapeutics. Data include:

Tri-specific vIgDs for treating cancer with a single domain capable of interacting with three different B7 family members. Depending on formatting, tri-specific vIgDs are potentially capable of agonizing CD28, blocking PD-L1, blocking CTLA-4, and/or depleting tumor cells and/or regulatory T cells. Initial formats investigated in an animal model of cancer demonstrated activity with tumor growth suppression.
A dual ICOS/CD28 costimulatory vIgD fused with the HER2-targeting monoclonal antibody trastuzumab to provide immune stimulation in the tumor microenvironment. These V-mAbs demonstrated in vitro proof of principle for immune cell stimulation and proliferation in response to HER2-positive tumor cells.
Multiple vIgD Fc fusions capable of targeting TIGIT and PD-1 while sparing CD226. These multi-checkpoint inhibitory molecules blocked checkpoint activity and improved IFN-γ production by "exhausted" T cells.
"The SITC (Free SITC Whitepaper) data suggest the versatile vIgD platform has the potential to contribute to the next generation of immuno-oncology therapeutics. Based on these and other encouraging preclinical data, we are continuing to identify and develop appropriate candidates from our vIgD platform for clinical trials for both oncology and inflammation," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine.

On November 10, 2017 Nektar Therapeutics (Nasdaq: NKTR) reported that its corporate presentation will be webcast at the upcoming Jefferies 2017 London Healthcare Conference in London on Wednesday, November 15, 2017 at 10:00 a.m. GMT (Press release, Nektar Therapeutics, NOV 10, 2017, View Source [SID1234521926]).

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The presentation will be accessible via a Webcast through a link posted on the Investors, Events Calendar section of the Nektar website: View Source This Webcast will be available for replay until December 11, 2017.

On November 10, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that two of its cancer immunotherapies demonstrated antigen-specific T-cell stimulation in phase 1 studies. INO-3112 (now called MEDI0457), an investigational T-cell activation immunotherapy that targets cancers caused by human papillomavirus (HPV) types 16 and 18 and licensed to MedImmune, the global Research and Development arm of AstraZeneca, also led to a head and neck cancer patient’s complete response when matched with a PD-1 checkpoint inhibitor (Press release, Inovio, NOV 10, 2017, View Source [SID1234521931]). In addition, INO-1400, Inovio’s investigational cancer immunotherapy targeting hTERT, which is over-expressed in a majority of cancers, generated hTERT-specific IFN-γ secreting T cells, suggesting an ability to break immune tolerance. These results were revealed at poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 32nd Annual Meeting starting today at National Harbor, Md.

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Dr. J. Joseph Kim, Inovio’s President and CEO, said, "This study of MEDI0457 shows efficacy signals that Inovio’s activation immunotherapy coupled with checkpoint inhibitor could have meaningful therapeutic impact, given an unusual complete response in one patient. Separately, we are evaluating our hTERT therapy, INO-1400, in nine different solid tumors including breast, lung and pancreatic cancers in a clinical study. Any success we see in our hTERT therapy gives us added confidence in our recently initiated efficacy studies combining PD-1/PD-L1 inhibitors and INO-5401, which includes three of Inovio’s top SynCon cancer antigens – hTERT, WT1, and PSMA, which are over-expressed in multiple tumor types. We look forward to sharing further data on our immunotherapies as studies progress."

In a phase 1 study of MEDI0457 in 22 HPV-positive patients with squamous cell carcinoma of the head and neck, Inovio has previously demonstrated that this cancer immunotherapy generated robust antigen-specific CD8+ killer T cell responses in both tumor tissue and peripheral blood. One patient which initially displayed a slight increase in T cell immune responses developed progressive disease at 11 months into the study and received nivolumab, a PD-1 checkpoint inhibitor. Subsequently, the patient had a sustained complete response after only four doses, and continues on therapy with no evidence of disease, 16 months after initiation of nivolumab.

Detailed immune analyses found that MEDI0457 had activated HPV16-specific CD8+ T cells in the patient and the subsequent treatment with nivolumab helped to unleash the expansion of these killer T cells, which is contributing to the sustained complete response observed in this patient. Medimmune is conducting a separate phase 1/2 trial combining its PD-L1 inhibitor (durvalumab) with MEDI0457 in HPV-associated head and neck cancer patients to evaluate the clinical efficacy of the combination treatment.

Dr. Charu Aggarwal, MD, MPH, medical oncologist and assistant professor of medicine at the hospital of the University of Pennsylvania and the principal investigator of this study, said "This observation suggests that treatment with MEDI0457 prior to PD-1 inhibition can be synergistic, and increase efficacy of checkpoint inhibitors."

In Inovio’s phase 1 dose-escalation study of its synthetic optimized DNA plasmids that target hTERT, the immunotherapies were administered via Inovio’s CELLECTRA delivery device to assess the safety, tolerability, and immune effects of INO-1400 or INO-1401 (two different versions of HTERT constructs), alone or co-administered with a plasmid encoding for IL-12 (INO-9012), in 90 patients with 9 different solid tumors. Interim results presented at the conference show positive safety and tolerability data as well as the generation of hTERT-specific IFN-γ secreting T cells, suggestive of an ability to break immune tolerance.

Dr. Robert Vonderheide, MD, DPhil, Director of the Abramson Cancer Center of the University of Pennsylvania and a principal investigator for the study, said: "If successful, this vaccine platform could represent not only a novel type of immune therapy for cancer patients, but also one day offer an opportunity for immune prevention of cancer."

High levels of human telomerase reverse transcriptase (hTERT) have been reported in many tumor types such as breast, lung, and pancreas. Inovio’s hTERT therapy may prove to be a promising immuno-oncology target for the treatment of these cancers. In 2017, over 530,000 new cases of breast, lung, or pancreatic cancers were reported in the United States and over 240,000 people died from these cancers. Despite available treatments, mortality rates remain unacceptably high in these tumor types. In addition, many existing treatment modalities are associated with significant adverse events.

On November 9, 2017 LIDDS reported that it has entered a research collaboration with the Department of Laboratory Medicine at Karolinska Institute, Sweden (Press release, Lidds, NOV 9, 2017, View Source [SID1234555923]). The collaboration regards fundamental preclinical studies on formulations based on the NanoZolid technology, as well as access to risk laboratories for formulation development.

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LIDDS broadens its R&D activities to develop novel NanoZolid formulations for local tumor therapy by establishing a collaboration with Professor Mustapha Hassan and Dr. Ying Zhau at the Department of Laboratory Medicine (LABMED) at Karolinska Institute in Huddinge.

– LIDDS appreciate very much the collaboration with KI, and I am confident that the ongoing collaborative research will be fruitful and supportive to develop new efficient formulations with the NanoZolid technology. We are also pleased with the preclinical expertise that we have encountered at the Department Laboratory Medicine at Novum, states CEO of LIDDS Monica Wallter.
The collaboration includes fundamental preclinical studies and gives access to risk laboratories for formulation development with hazardous substances. Within the frame of the collaboration, novel NanoZolid formulations will be investigated prior to entering the clinical phase.

BioTime has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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