On April 2, 2019 LIDDS AB reported that Clinical data shows that intratumoral delivery of TLR agonists in combination with immune checkpoint inhibitors can effectively treat solid cancers (Press release, Lidds, APR 2, 2019, View Source [SID1234555907]). NanoZolid technology is very suitable to provide sustained intratumoral release and minimize the need for repeated injections. LIDDS has performed pre-clinical studies with promising results using a TLR9 agonist formulated with NanoZolid.

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Toll-like receptors (TLR) are a key target for the pharmaceutical industry in the fight against cancer. TLRs are expressed on various immune cells, including dendritic cells, and they initiate the body’s immune response. TLR activation can lead to an immunologically active or inflamed tumor environment which then recruits the cytotoxic T-cells necessary for an anti-tumor response in immunotherapy.

-The NanoZolid technology addresses key issues in developing TLR agonists as repeated intratumoral injections are needed using standard formulations, says Monica Wallter, CEO LIDDS.

-We will be focusing our project on TLR9, one of the most promising targets for increasing response and reversing resistance to immunotherapies. TLR9 agonists have been shown to be most effective when injected directly into a tumor, says Monica Wallter.

-A preclinical programme is ongoing to broaden the results obtained to date and we are now preparing for a Phase I clinical trial using NanoZolid combined with a TLR9 agonist. The first human study is planned to commence in 2020, says Monica Wallter.

Preclinical studies have shown that activation of TLR pathways can lead to potent immunological effects that generate anti-tumor immunity and shrink tumors. Most importantly, these effects can act in synergy with immune checkpoint inhibitors.

-There is significant commercial potential in this area of research and drug development and the market for TLR agonists is expected to be worth hundreds of millions of dollars over the coming years, says Monica Wallter.

The most relevant target cancers for the TLR9 project are head and neck cancer, prostate cancer and lymphomas. These cancers are diagnosed in around 2 million patients each year.

Toll-like receptors have been studied for many years and the emerging clinical data suggests that their time has come as important anti-cancer agents when used in combination with immune checkpoint inhibitors.

On April 2, 2019 Nordic Nanovector ASA (OSE: NANO) reported that promising results from its preclinical research collaboration to develop a novel CD37-targeting alpha therapy for B-cell tumours have been reported today in an oral presentation at TAT11, the 11th International Symposium on Targeted-Alpha-Therapy (1-4 April, Ottawa, Canada) (Press release, Nordic Nanovector, APR 2, 2019, View Source [SID1234553453]).

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The research collaboration with Orano Med (formerly known as AREVA Med) was established in June 2016 to develop and investigate a next-generation targeted alpha therapy comprising Nordic Nanovector’s chimeric anti-CD37 antibody (NNV003) and the alpha-particle-generator lead-212 (212Pb) for the treatment of B-cell malignancies.

The results reported in an oral presentation given today describe promising findings from preclinical studies investigating the tolerability and dose-dependent efficacy of 212Pb-NNV003 in mouse models of chronic lymphocytic leukaemia (CLL) and Burkitt’s lymphoma (a type of non-Hodgkin’s lymphoma, NHL).

In the studies, 212Pb-NNV003 displayed a favourable toxicity profile after a single intravenous injection. In one study, 100% of mice with tumour xenografts were alive five months after the injection of 212Pb-NNV003, while only 50% of control mice receiving cold antibody where alive after 1.5 months.

Jostein Dahle, Chief Scientific Officer of Nordic Nanovector, said: "Our research collaboration with Orano Med continues to produce promising preclinical results and provides an early demonstration of the potential of 212Pb-conjugated CD37-targeted alpha therapy to treat leukaemias and lymphomas where there is no substantial tumour mass and tumour cells are near healthy tissues. This approach also may prove useful for CLL and NHL patients who have relapsed or become refractory to standard CD20-targeting agents that are used in front-line therapy. We look forward to further results from this research programme."

The oral presentation entitled 212Pb-NNV003 as a Novel Targeted Alpha Therapy for CD37 Positive B-cell Chronic Lymphocytic Leukaemia (CLL) and Non-Hodgkin’s Lymphoma (NHL) was given by Dr A. Saidi of Orano Med.

On April 2, 2019 Alligator Bioscience (Nasdaq Stockholm: ATORX), reported that new preclinical data on the drug candidate ATOR-1144 will be presented at the scientific conference AACR (Free AACR Whitepaper) (American Association for Cancer Research), held in Atlanta on March 29 – April 3, 2019 (Press release, Alligator Bioscience, APR 2, 2019, View Source [SID1234538667]). ATOR-1144 is a first-in-class bispecific tumor-localized antibody targeting the checkpoint inhibitor CTLA-4 and the co-stimulatory receptor GITR (Glucocorticoid-Induced TNFR family Related).

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The new preclinical data demonstrate that ATOR-1144 works through several pathways: activation of effector T cells, depletion of regulatory T cells (Tregs) and tumor cells and activation of NK (natural killer) cells, with potential for enhanced tumor cell killing. In addition, GITR is shown to be expressed on tumor-infiltrating lymphocytes and neoplastic cells in tumor samples from e.g. head and neck, esophageal, ovarian cancer, melanoma and B and T cell lymphoma, allowing for direct tumor cell killing.

"We are excited to present ATOR-1144 to the scientific community. It is a novel tumor-localizing CTLA-4 bispecific antibody with the potential for enhanced immune-activation of both the adaptive and the innate immune system, as well as direct anti-tumor effects. These properties are likely to act in concert and give ATOR-1144 the potential for superior efficacy", said Per Norlén, CEO of Alligator Bioscience.

Dr Anne Månsson Kvarnhammar, Senior Scientist at Alligator, will present a poster (#4077) with the title: "ATOR-1144 is a tumor-directed CTLA-4 x GITR bispecific antibody that acts by depleting Tregs and activating effector T cells and NK cells" on Tuesday, April 2, 1:00 p.m. EDT (7:00 p.m. CEST). The poster will then be available on View Source

For further information, please contact:
Cecilia Hofvander, Director Investor Relations & Communications
Phone +46 46 540 82 06
E-mail: [email protected]

This information is such information as Alligator Bioscience AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 1:30 p.m. CEST on April 2, 2019.

About ATOR-1144
ATOR-1144 is a bispecific IgG1 antibody drug candidate targeting both CTLA-4 and GITR. It is a combination of a GITR specific antibody isolated from ALLIGATOR-GOLD, while the CTLA-4 part was developed by FIND optimization of CD86, a natural CTLA-4 ligand.

On April 2, 2019 Massive Bio, Inc., a leader in providing simplified and affordable access to clinical trials and precision oncology to cancer patients treated at community-based oncology practices, reported that its Trials-in-Progress poster titled "SYNERGY-AI: Artificial intelligence based precision oncology clinical trial matching and registry" will be presented by Dr. Selin Kurnaz, a lead investigator, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, GA, USA, during the Phase I-III Trials in Progress session on April 2nd, 2019 (Press release, Admera Health, APR 2, 2019, View Source [SID1234537386]).

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The poster (Abstract #CT218), View Source!/6812/presentation/10031 discusses the ongoing, pivotal global registry for cancer patients evaluating the feasibility and clinical utility of an Artificial Intelligence-based precision oncology clinical trial matching tool powered by a virtual tumor board (VTB) program. The SYNERGY-AI registry is the first of its kind to combine artificial intelligence, genomic biomarkers and multi-variate analysis to accelerate clinical trial matching and promote access to promising cancer therapies.

"We continue active enrollment in this innovative precision oncology and artificial intelligence project, and we are honored and excited to be among the highly selected group of clinical trials to be presented at AACR (Free AACR Whitepaper). Moreover, we are the only company in the market that operationalizes technology – we not only pre-screen patients, we find sites to the patients, eliminate insurance barriers and truly close the last mile in oncology clinical trial enrollment. We clean massive operational inefficiencies and we are making a leap frog in clinical research," said Selin Kurnaz, PhD., CEO and Co-Founder of Massive Bio.

In addition, today, Massive Bio and Admera Health announced a non-exclusive collaborative agreement as active participants in SYNERGY-AI registry. Under the terms of the agreement, Massive Bio and Admera Health will focus on real world evidence, biomarker data and clinical trial matching in precision oncology studies. In addition, Admera Health also provides genomics and bioinformatics services to customers wishing to conduct research in a CLIA environment.

"By combining the expansive technology and precision oncology capabilities of Massive Bio with Admera Health’s specialization in genomics and bioinformatics, we hope to develop and provide the next wave of molecular-based portfolio of technology innovations and services," stated Jeffrey R. Mitchell, Associate Director of Strategy and Marketing of Admera Health. Mitchell continued, "In addition, given the geographic strengths of our respective companies, there will also be opportunities to expand clinical trials using each other’s proprietary technology around the globe."

Commenting on the announcement, Chief Medical Advisor and Co-Founder of Massive Bio Inc., Dr. Arturo Loaiza-Bonilla, MD, MSEd, stated, "Massive Bio’s Artificial Intelligence technology platform is extremely well positioned to enable just-in-time clinical trial matching and enrollment, with a targeted therapy and immunotherapy focus, and is proven to accelerate access to innovative therapies, sponsor and CRO efficiency, as well as time to market. We certainly welcome collaborations with all stakeholders in the diagnostics and research space, aiming to close existing gaps in cancer research." Chief Business Officer of Massive Bio Inc, Harry Buchman also stated, "With a growing number of successful development applications, it is our goal to continue to promote precision oncology approaches at the point-of-care, and to ease access to clinical trials, while reducing patient and provider burden and overall cancer care costs."

About the Study

The SYNERGY-AI Registry is an international prospective, observational cohort study of adult and pediatric patients with advanced solid and hematological malignancies. Using a proprietary application programming interface (API) linked to existing electronic health records (EHR) platforms, individual clinical data is extracted, analyzed and matched to a parametric database of existing institutional and non-institutional CT. Machine learning algorithms allow for optimized matching based on CT allocation and availability. Enrollment is ongoing, with a target of ?1,500 patients. Please refer to View Source for details.

On April 2, 2019 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported new clinical data on vopratelimab (JTX-2011) at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, GA (Press release, Jounce Therapeutics, APR 2, 2019, View Source [SID1234535387]). The Jounce poster presentations show that patients in the ICONIC trial with emergence of ICOS hi CD4 T cells have improved progression free survival (PFS) and overall survival (OS) compared to patients with ICOS lo CD4 T cells. Data related to important immune characteristics of ICOS hi CD4 T cells were also presented.

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"We are pleased to see our initial observations of tumor reductions associated with ICOS hi CD4 T cells now extend to improved PFS and OS. All observed benefit in the study was in the group of patients that showed emergence of these cells. As vopratelimab, and not PD-1 inhibitors, is responsible for the emergence of the ICOS hi CD4 cells, we are using this key translational data to guide our next steps in development," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "We have further characterized the ICOS hi CD4 T cells as activated T effector cells by flow cytometry and gene expression profiling and demonstrated peripheral expansion of T cell receptor (TCR) clones originally found in the matched archival tumor. These characteristics provide additional scientific support for clinical study designs based on the emergence of ICOS hi CD4 T cells."

In a poster titled "Improved progression-free and overall survival (PFS/OS) in patients (pts) with emergence of JTX-2011 (vopratelimab) associated biomarker (ICOS high CD4 T cells) on the ICONIC trial," the ICONIC investigators and Jounce scientists describe the baseline characteristics and clinical outcomes of patients with emergence of ICOS hi CD4 T cells as compared to patients who did not develop this T cell population.

Three groups of ICONIC relapsed refractory solid tumor patients were compared in the new analysis: 1) 18 patients who have demonstrated ICOS hi CD4 T cells in the blood, 2) 32 patients who have demonstrated ICOS lo CD4 T cells, and 3) a group of patients enrolled in parts A through D which includes an additional 151 patients that were not tested for ICOS status due to lack of samples ("All Patients"). The analyses revealed:

The emergence and persistence of the ICOS hi CD4 T cell biomarker in the peripheral blood is associated with improved PFS and OS:
All benefit in the study, measured by tumor reductions, PFS and OS, was in the ICOS hi CD4 T cell group
PFS: median 6.2 months for patients with ICOS hi CD4 T cells vs 2 months for both patients with only ICOS lo CD4 T cells and All Patients
OS: median not yet reached for patients with ICOS hi CD4 T cells vs 9 months for patients with only ICOS lo CD4 T cells and 9.1 months for All Patients
The emergence of ICOS hi CD4 T cells is attributed to vopratelimab and not PD-1 inhibitors
There is no association of ICOS hi CD4 T cells with the common predictive biomarkers microsatellite instability-high (MSI-H), tumor mutation burden (TMB) or PD-L1 immunohistochemistry (IHC)
The ICOS hi CD4 T cell group included PD-1 naive and experienced patients across multiple solid tumor types
In a poster titled "Genetic and molecular profiling of ICOS hi CD4 T cells demonstrates clonal expansion of TH1 effector cells following vopratelimab (JTX-2011) treatment in subjects with solid tumors," Jounce researchers describe the characteristics of ICOS hi CD4 T cells associated with vopratelimab treatment, including:

Vopratelimab stimulates CD4 T cells with pre-existing high levels of ICOS
Peripheral TCR clones associated with the original matched tumor are expanded in patients with emergent ICOS hi CD4 T cells
ICOS hi CD4 T cells are not T regulatory cells and display distinct characteristics of activated T effector cells by both flow cytometry and transcriptional profiling
"We are encouraged by the improved PFS and OS data associated with the emergence of the ICOS hi CD4 T cell biomarker and are convinced that meaningful advancements in immuno-oncology will require the type of science-based translational understandings that the Jounce team and platform have enabled to advance vopratelimab thus far," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "We have established our translational technology base for the purpose of creating a preclinical and, more importantly, clinical scientific understanding of the mechanism of action of new immunotherapies and the characteristics of responding versus non-responding patients to focus the next steps of clinical development for vopratelimab and our pipeline."

The posters are available on the "Our Approach" section of the Jounce Therapeutics website at www.jouncetx.com.

Jounce Therapeutics to Host Event and Webcast
Jounce Therapeutics will host an investor and analyst event beginning at 6:30 p.m. ET and live webcast beginning at 7:00 p.m. ET, on Tuesday, April 2, 2019. To access the live webcast, please visit the "Events & Presentations" page in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days thereafter.

About Vopratelimab (JTX-2011)
Jounce’s lead product candidate, vopratelimab, is a monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO­Stimulator, a protein on the surface of certain T cells. The company is developing vopratelimab to treat solid tumors as a single agent and in combination with other therapies.

About the ICONIC Trial
The ICONIC trial is an adaptive, open label, dose escalation and expansion clinical study of vopratelimab alone and in combination with nivolumab, ipilimumab and pembrolizumab in patients with advanced solid tumors.