On April 17, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has launched atezolizumab, a recombinant humanized anti-PD-L1 monoclonal antibody, (brand name, "TECENTRIQ Intravenous Infusion 1200 mg;" hereafter, "TECENTRIQ") for the treatment of "unresectable advanced or recurrent non-small cell lung cancer (NSCLC) today (Press release, Chugai, APR 17, 2018, View Source [SID1234525488]). TECENTRIQ received a manufacturing and marketing approval on January 19, 2018 and was listed on the National Health Insurance (NHI) reimbursement price list today.

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"Cancer immunotherapy is expected to be a breakthrough therapy which may significantly change cancer treatment. As our mission is to deliver innovative therapeutic drugs to patients, it is a great pleasure for us to finally being able to launch TECENTRIQ," said Chugai’s President & CEO, Tatsuro Kosaka. "We will continue our research and development activities in multiple cancer types and combination therapies to realize sustained therapeutic effects and improvement of survival rate, as well as cure in more patients with cancer."

TECENTRIQ is an immune checkpoint inhibitor targeting PD-L1 (Programmed Death-Ligand 1) which is a protein expressed on tumor cells and tumor-infiltrating immune cells. PD-L1 blocks T-cell activity by binding with PD-1 and B7.1 receptors on T-cell surface. By inhibiting PD-L1, TECENTRIQ may enable the activation of T-cells and boost immune response against cancer cells.

In Japan, the annual prevalence of lung cancer is estimated to be approximately 128,700 in 2017 (male: 86,700, female: 42,000). The annual mortality of lung cancer, the leading cause of cancer deaths (the second leading cause in women) in Japan, is approximately 78,000 (male: 55,600, female: 22,400; predicted figure for 2017).*

As a top company in the field of oncology in Japan, Chugai firmly believes that the launch of TECENTRIQ in Japan as a new therapeutic option for the treatment of "unresectable advanced or recurrent NSCLC," will allow us to further contribute to treat patients and promote appropriate use of drugs.

On April 17, 2018 Elios Therapeutics, a biopharmaceutical company developing innovative particle-delivered, dendritic cell vaccines in oncology, reported initial open-label results from the ongoing Phase 2b clinical trial of the TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine in patients with stage III and IV (resected) melanoma (Press release, Orbis Health Solutions, APR 17, 2018, View Source [SID1234529911]). Results were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting held April 14-18, 2018 in Chicago, Illinois.

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"We are encouraged by these initial open-label results from our Phase 2b trial which demonstrate a compelling safety profile and provide early evidence that the TLPLDC vaccine may enhance the efficacy of commonly used FDA-approved systemic therapies, including checkpoint inhibitors," said George E. Peoples, M.D., chief medical officer at Elios Therapeutics. "We look forward to continuing our assessment of the TLPLDC vaccine in this ongoing study as we evaluate opportunities for further clinical development of combination therapies."

In an ongoing prospective, randomized, double-blind, placebo-controlled Phase 2b trial, patients with resected Stage III and IV melanoma were randomized (2:1) to received either TLPLDC vaccine or placebo to prevent recurrence. All patients who recurred on the trial (met study endpoint) were then offered open-label TLPLDC along with standard of care therapy as determined by the patient’s treatment team.

The initial open-label results presented were from 22 patients. Seven patients had their recurrences resected and were treated with the TLPLDC vaccine to prevent a second recurrence. At 12.5 months of median follow-up, only one patient has recurred.

The remaining 15 patients were on a variety of FDA-approved systemic therapies for their non-resectable recurrences. Of these patients, two patients withdrew from the study and one was not treated. In the remaining 12 patients treated with the TLPLDC vaccine in combination with their standard of care systemic therapy, two patients had a complete response (median follow-up 8.6 months), seven had stable disease and two had progressive disease. One patient progressed initially on TLPLDC vaccine alone but was converted to a complete response once checkpoint inhibitor therapy was initiated. Importantly, the addition of the TLPLDC vaccine did not increase the toxicity of checkpoint inhibitors, BRAF/MEK inhibitors, or TVEC in these patients.

To view the full abstract, please visit the AACR (Free AACR Whitepaper) website at View Source

About TLPLDC
The TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine is an autologous, personalized, therapeutic cancer vaccine designed to stimulate the immune system to recognize tumor cells and fight a patient’s specific cancer. TLPLDC is made from the patient’s own tumor cells and dendritic cells – the most potent antigen-presenting cells in the body. Once TLPLDC is injected, the tumor lysate-loaded dendritic cells present the tumor antigens to the immune system, stimulating the induction of tumor-specific, activated T cells that are able to find and destroy tumor cells that may remain in the body. TLPLDC is currently being studied as a monotherapy and in combination with standard of care checkpoint inhibitor therapy in a Phase 2b clinical trial for the treatment of late-stage melanoma at leading academic cancer centers in the United States.

On April 17, 2018 Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy, reported preclinical data on the immune activating antibody ATOR-1015 at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 taking place in Chicago, Illinois American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 taking place in Chicago, Illinois. ATOR-1015 is a first-in-class bispecific tumor-directed antibody, targeting CTLA-4 and OX40, designed to selectively activate the immune system in the tumor, without increasing systemic toxicity.

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The preclinical data demonstrate that ATOR-1015 physically localizes to the tumor and selectively activates the immune system in the tumor area, confirming the intended ATOR-1015 mechanism of action.

ATOR-1015 is primarily designed for combination therapy with a PD-1 blocking antibody, and the potential of this approach is supported with preclinical data reporting enhanced anti-tumor effect of ATOR-1015 in combination with an anti-PD-1 antibody, as compared to anti-PD-1 monotherapy. In addition, ATOR-1015 demonstrated superior efficacy compared to mono-targeting CTLA-4 and OX40 antibodies.

"The results presented in Chicago confirm that our CTLA-4 bispecific antibody ATOR-1015 selectively activates the immune system in the tumor area. This offers great potential for an improved benefit/risk profile for cancer patients. We are more and more excited about the significant prospects for this unique compound, particularly in combination with PD-1 blockers, and are looking forward to initiate clinical development later in the year", said Per Norlén CEO of Alligator Bioscience.

Alligator is planning to initiate an ATOR-1015 Phase I study during the second half of 2018.

A poster with the title "CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation" is showcased today at 8-12 a.m. EDT and is also available on the company web page View Source

For further information, please contact:
Cecilia Hofvander, Director Investor Relations & Communications
Phone +46 46 286 44 95
E-mail: [email protected]

The information was submitted for publication, through the agency of the contact person set out above, at 3 p.m. CEST on 17 April 2018.

The following is a roundup of presentations and findings from multiple companies participating in the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago (Press release, BioSpace, APR 17, 2018, View Source [SID1234525435]).

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H3 Biomedicine Inc. – Working with Foundation Medicine, H3 Biomedicine unveiled novel findings from a comprehensive genomic analysis of 6,235 patients across 15 hematologic malignancies at AACR (Free AACR Whitepaper). The results include the first-ever observance of recurrent RNA splicing factor mutations in non-Hodgkin’s lymphoma and multiple myeloma, the company said. In its announcement, H3 said the findings demonstrate the "continued emergence of splicing factor mutations as a hallmark of dozens of hematologic and solid tumor cancers, their potential role in tumor formation and growth, and, thus, the opportunity to advance a new class of therapies."
Checkmate Pharmaceuticals – Data from an ongoing Phase Ib trial shows that Checkmate’s Toll-like receptor 9 CMP-001 combined with Merck’s Keytruda demonstrated "deep and durable clinical responses" in patients with advanced melanoma who are resistant to prior anti-PD-1 checkpoint inhibition. Data shows that the combination therapy brought about the systemic regression of "non-injected cutaneous, nodal, hepatic, and splenic metastases in patients who had progressed on a median of two prior therapies."

Deciphera Pharmaceuticals – Cambridge, Mass.-based Deciphera unveiled preclinical data that showed DCC-2618, a KIT and PDGFRα kinase switch control inhibitor, inhibited primary and secondary KIT mutations and primary PDGFRα mutations in gastrointestinal stromal tumors (GIST) and systemic mastocytosis. Deciphera said in comparison to other approved compounds, DCC-2618 demonstrated the "broadest profile of inhibition" in the preclinical study.
NewLink Genetics – In a poster presentation at AACR (Free AACR Whitepaper) NewLink showed that indoximod has a unique method of action in modulating AhR-driven transcription of genes. The company said the different mechanism of action may contribute to antitumor immune responses in the IDO pathway, as well as independent of that IDO pathway. The company said indoximod regulates the "differentiation of helper T cells toward an immuno-stimulatory helper function and downregulates genes that control the differentiation of T cells into immuno-suppressive regulatory T cells in an AhR dependent manner."

Torque – Preclinical data presented by Torque at AACR (Free AACR Whitepaper) shows the company’s Deep-Primed IL-15 and Deep-Primed IL-12 cellular therapy programs demonstrated superior activity compared to systemically administered IL-15 and IL-12. Torque’s Deep-Primed therapeutics use material engineering to anchor immune-stimulatory drugs directly to the surface of multi-targeted, antigen-primed T cells. This allows the activation of the adaptive and innate immune system with pharmacologic control in the tumor microenvironment, according to the company.
Laboratory for Advanced Medicine – With a push to advance early cancer diagnostics California-based Laboratory for Advanced Medicine revealed data that demonstrates the utility of circulating tumor DNA (ctDNA) methylation markers in the diagnosis, surveillance and prognosis of Hepatocellular Carcinoma. In an AACR (Free AACR Whitepaper) presentation, the company said the findings support that "ctDNA carrying cancer-specific genetic and epigenetic aberrations may enable a non-invasive liquid biopsy for the diagnosis and monitoring of cancer."
PharmaMar – New data presented by PharmaMar at AACR (Free AACR Whitepaper) showed that plitidepsin interacts with and inhibits PKR on the eEF1A2 enzyme. Plitidepsin inhibits this interaction obtaining the induction of cell death, the company announced. PharmaMar said through the bonding to eEF1A2, plitidepsin annuls the oncogenic properties of its target.

On April 17, 2018 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205), a late clinical-stage nanomedicine company pioneering new approaches to the local treatment of cancer, reported that preclinical data evaluating the activation of the cGAS-STING pathway by NBTXR3 has been presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in Chicago, Illinois (April 14-18, 2018) (Press release, Nanobiotix, APR 17, View Source [SID1234525489]).

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NBTXR3 is a first-in-class product designed to destroy, when activated by radiotherapy, tumors and metastasis
through physical cell death and to induce immunogenic cell death leading to specific activation of the immune
system.
Establishing how NBTXR3, activated by radiotherapy, impacts and primes the immune response against tumor
cells is central to Nanobiotix’s immuno-oncology program. Recently, the cGAS-STING pathway has emerged as
the key component of the anti-tumor immune response, along with immunogenic cell death. Therefore,
evaluation of the impact of NBTXR3 on this conserved signaling cascade is essential.

Dr Elsa Borghi, CMO, commented, "cGAS-STING activation is of fundamental importance in establishing an
adaptive anti-tumor immune response. These encouraging preliminary results suggest that NBTXR3 activated by
radiotherapy could increase the activation of this pathway, compared to radiotherapy alone."
"Activation of the cGAS-STING pathway by NBTXR3 nanoparticles exposed to radiotherapy"
J. Marill, N. Mohamed Anesary, A. Darmon, P. Zhang and S. Paris.
Poster number #4571
In this poster, Nanobiotix presents data showing a dose-dependent increase in cGAS-STING pathway activation
with NBTXR3 activated by radiotherapy through both in vitro and in vivo analyses.
In vitro analyses show a significant increase in luciferase activity (reflecting the transcriptional activity of IRF) was
observed in HCT116-DUAL cells treated with NBTXR3 plus RT, compared to radiotherapy alone. Further,
NBTXR3 activated by radiotherapy triggers an increased generation of micronuclei (involved cGAS-STING
response) compared to radiotherapy alone.
In vivo, NBTXR3 activated by radiotherapy leads to a greater production of IFN-b and overexpression of its gene,
compared to radiotherapy alone.
Previous work has demonstrated that NBTXR3 activated by radiotherapy increased cancer cell killing efficiency
along with Immunogenic Cell Death (ICD), compared to radiotherapy alone. Here, in vitro data generated from
HCT116-DUAL and in vivo data from CT26 tumors further demonstrate that NBTXR3 activated by radiotherapy
is able to trigger a stronger activation of the cGAS-STING pathway, compared to radiotherapy alone, even in
combination with the STING agonist 2’,3’-cGAMP. Moreover, NBTXR3 can maximize the effect of 2’,3’-cGAMP,
the natural agonist of STING, when activated by the radiotherapy.
These observations support the rationale for using NBTXR3 with radiation therapy in combination with
immunotherapeutic agents and/or STING agonist to transform tumors into an in-situ cancer vaccine.
These results, obtained in human and mouse colorectal cancer cells models, could have a very positive impact
on the anti-tumoral immune response, potentially transforming non-responding tumors into responding, i.e.
turning them from "cold" to "hot".
NBTXR3 positioning in IO
Many IO combination strategies focus on ‘priming’ the tumor, which is now becoming a prerequisite of turning
a "cold" tumor into a "hot" tumor.
Compared to other modalities that could be used for priming the tumor, NBTXR3 could have a number of
advantages: the physical and universal mode of action that could be used widely across oncology, a one-time
local injection and good fit within existing medical practice already used as a basis for cancer treatment, as well
as a very good chronic safety profile and well-established manufacturing process.
Published preclinical and clinical data indicate that NBTXR3 could play a key role in oncology and could become
a backbone in immuno-oncology.
Nanobiotix’s immuno-oncology combination program opens the door to new developments, potential new
indications, and important value creation opportunities.
***
About American Association for Cancer Research (AACR) (Free AACR Whitepaper) www.aacr.org
The AACR (Free AACR Whitepaper) Annual Meeting is one of the main international oncology events highlighting the best cancer science and medicine
from institutions all over the world. The American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in Chicago,
Illinois (April 14-18, 2018).
About NBTXR3
NBTXR3 is a first-in-class product designed to destroy, when activated by radiotherapy, tumors and metastasis through
physical cell death and to immunogenic cell death leading to specific activation of the immune system.
NBTXR3 has a high degree of biocompatibility, requires one single administration before the whole radiotherapy treatment
and has the ability to fit into current worldwide standards of radiation care.
NBTXR3 is being evaluated in head and neck cancer (locally advanced squamous cell carcinoma of the oral cavity or
oropharynx), and the trial targets frail and elderly patients who have advanced cancer with very limited therapeutic options.
The Phase I/II trial has already delivered very promising results regarding the local control of the tumors and a potential
metastatic control through in situ vaccination.
Nanobiotix is running an Immuno-Oncology program with NBTXR3 that includes several studies. In the U.S., the Company
received the FDA’s approval to launch a clinical study of NBTXR3 activated by radiotherapy in combination with anti-PD1
antibodies in lung, and head and neck cancer patients (head and neck squamous cell carcinoma and non-small cell lung
cancer). This trial aims to expand the potential of NBTXR3, including using it to treat recurrent or metastatic disease.
The first market authorization process (CE Marking) is ongoing in Europe in the soft tissue sarcoma indication.
The other ongoing studies are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally
advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with
concurrent chemotherapy, and prostate adenocarcinoma.