On April 1, 2019 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that new preclinical data from the Company’s innovative portfolio of next generation immunotherapies has been presented in a conference session by Pr. Eric Vivier, Chief Scientific Officer, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held from March 29–April 3, in Atlanta (Press release, Innate Pharma, APR 1, 2019, View Source [SID1234534820]).

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Eric Vivier, Chief Scientific Officer of Innate Pharma, said:"Innate Pharma has always been driven by scientific leadership and we are very proud to present new preclinical data from our broad and innovative portfolio of next generation cancer immunotherapies. For the first time, we also shared data from our multi-specific NK-cell engager technology that highlight a new generation of molecules for fighting cancers."

While chairing the conference session"Innate Immunity and Complement in Solid Tumors", the following findings were presented by Eric Vivier in a lecture titled "Targeting innate immunity in next generation cancer immunotherapies" yesterday at AACR (Free AACR Whitepaper):

IPH5201 (anti-CD39) and IPH5301 (anti-CD73), targeting the adenosine pathway:

CD39 and CD73 are membrane-bound extracellular enzymes which play a major role in promoting immunosuppression through the pathway degrading adenosine triphosphate (ATP) into immunosuppressive adenosine (Ado). The blockade of CD39 and CD73 has the potential to promote anti-tumor immune responses across a wide range of tumors.

New data demonstrate that a combination of Innate Pharma’s anti-CD39 monoclonal antibody, IPH5201, and ATP-inducing oxaliplatin had a synergistic effect that improved the control of tumor growth in a preclinical mouse model.

Previous findings showed that IPH5201 enhances the stimulatory effect of ATP on antigen presenting cells and abrogates the suppressive effect of ATP-derived Ado on the proliferation of T cells from healthy donors and cancer patients. In October 2018, Innate Pharma and AstraZeneca entered into a development collaboration and option for further co-development and co-commercialization for IPH5201.

New data from a crystal structure of the CD73/IPH5301 complex support a model for the differentiated mode of action of IPH5301 and enhanced efficacy compared to competitors. Analysis by electron microscopy revealed that the IPH5301 monoclonal antibody interacts mainly with CD73 dimer in an intra-dimer mode, constraining the CD73 enzyme in an inactive state in which AMP could not be hydrolyzed, in contrast to other antibodies in development that interact in an inter-dimer mode. Findings presented at the 2018 American Association of Cancer Research (AACR) (Free AACR Whitepaper) conference demonstrated that IPH5301 is more potent in vitrothan benchmark anti-CD73 antibodies currently under clinical development, on both membrane-bound and soluble CD73, in enzymatic activity as well as T cell proliferation assays.

Innate expects INDs to be filed for IPH5201 in the second half of 2019 and for IPH5301 in the first half of 2020.

First-in-class trifunctional NKCEs create a new generation of molecules for fighting cancer:

Innate Pharma’s proprietary multifunctional NKCE technology targets two activating receptors, NKp46 and CD16, on NK cells and a tumor antigen on cancer cells.

New pre-clinical data outlined in the presentation demonstrate that these first-in-class trifunctional NKCEs are more potent in vitroand in vivo than clinical therapeutic monoclonal antibodies targeting the same tumor antigen, such as rituximab, obinituzumab or cetuximab, with nooff-target effects. The data also demonstrate that co-engagement of NKp46 synergizes with CD16 to potentiate both tumor cell lysis and NK cell activation.

NKCEs stimulate NK cells instead of T cells and have been designed to improve the benefit-risk profile for the treatment of solid tumors.

Innate Pharma has a research collaboration and licensing agreement with Sanofi for the generation and evaluation of up to two multifunctional NK cell engagers, using both Innate Pharma’s and Sanofi’s technology and tumor targets. Under the terms of the license agreement, Sanofi is responsible for the development, manufacturing and commercialization of products resulting from the research collaboration. Innate Pharma is eligible for up to €400m in development and commercial milestone payments as well as royalties on net sales.

On April 1, 2019 Apollomics, Inc. (the "Company"), an innovative biopharmaceutical company committed to the discovery and development of oncology combination therapies, reported positive data for the Company’s multi-kinase inhibitor, APL-102, as both a single agent and in combination with an anti-PD-1 antibody in multiple preclinical studies (Press release, Apollomics, APR 1, 2019, View Source [SID1234534819]).

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"Our preclinical data presented today demonstrates a mechanism of action for APL-102 anti-tumor activity and a synergistic effect of the agent when combined with a check-point inhibitor (CPI)," said Sanjeev Redkar, PhD, President. "APL-102 treatment increased the total T-cells and the CD8 T-cells, and significantly decreased macrophages in the tumor, both as a single agent and in combination with an anti-PD1 antibody. We see a potential path forward for the agent as a single agent or in combination with CPIs which may improve the efficacy of APL-102 and broaden the efficacy of CPIs."

The studies, in multiple murine models, evaluated the effect of anticancer therapies that target components within the tumor microenvironment (TME) as opposed to the tumor itself. Colony stimulating factor 1 receptor (CSF-1R) was a key target as a means of controlling tumor associated macrophages in the TME. As a monotherapy, the results demonstrated that APL-102 inhibits CSF-1R in a radiometric enzyme activity assay with an IC50 of 43nM, and that APL-102 inhibited growth in cells dependent on CSF1-CSF1R signaling. APL-102 also demonstrated targeting of Vascular Endothelial Growth Factor Receptors (VEGFR) dependent angiogenesis and the Mitogen-Activated Protein Kinases (MAPK) pathway.

When APL-102 was given in combination with an anti-PD1 antibody, the results produced a more robust response than either single agent alone in syngeneic mouse models, which was associated with macrophage inhibition in the TME.

About APL-102

APL-102 is an oral, small molecule multi-kinase Inhibitor targeting several key oncogenic drivers. APL-102 inhibits both receptor tyrosine kinase (RTKs) and serine/threonine-kinases, including: angiogenesis via Vascular Endothelial Growth Factor Receptors (VEGFR) and Platelet-Derived Growth Factor Receptors (PDGFR); Mitogen-Activated Protein Kinases (MAPK) pathway via B-RAF and C-RAF; and, RET, CSF1R, DDR1 (discoidin domain receptor tyrosine kinase 1) and c-KIT. APL-102 is currently in preclinical, IND-enabling studies. The agent has demonstrated broad and potent antitumor activity in patient derived xenografts of liver cancer, breast cancer, colorectal cancer, gastric, esophageal and non-small cell lung cancer models with excellent oral bioavailability, biopharmaceutical properties, and a well-tolerated safety profile in a chronic safety study. Apollomics retains worldwide rights to APL-102.

On April 1, 2019 Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported that its Phase 1/2 immuno-oncology trial in patients with newly diagnosed glioblastoma (GBM) has completed its enrollment three months ahead of schedule (Press release, Inovio, APR 1, 2019, View Source [SID1234534818]). The 52-patient trial is designed to evaluate Inovio’s INO-5401 T cell activating immunotherapy encoding multiple antigens expressed by GBM and INO-9012, an immune activator encoding IL-12, in combination with cemiplimab-rwlc (also known as Libtayo or REGN2810), a PD-1 inhibitor developed by Regeneron Pharmaceuticals in collaboration with Sanofi. This trial information will be presented today at Phase I-III Trials in Progress session at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) being held in Atlanta.

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Inovio expects to report interim results from this study before the end of this year evaluating safety, immunological impact, progression-free survival and overall survival (see www.clinicaltrials.gov, identifier NCT03491683).

Dr. J. Joseph Kim, Inovio’s President and Chief Executive Officer, said, "We sincerely thank the patients and their doctors for participating in our innovative combination trial. This is an important step for Inovio’s cancer combination strategy using our T cell-generating therapies in combination with PD-1/PD-L1 inhibitors for GBM and for multiple other cancers to improve overall efficacy of immunotherapy. We have previously shown in a Phase 1 head and neck cancer clinical study, combining Inovio’s T cell-generating immunotherapy MEDI0457 along with checkpoint inhibitors have resulted in two complete responders who remain cancer free for over two years. In this GBM trial, our goal is to increase the overall survival of patients facing a disease where neither the standard of care, nor clinical outcomes have changed in a clinically significant way in more than a decade."

Inovio holds clinical partnerships with AstraZeneca for MEDI0457 (in HPV-related cancers) and collaborations with Roche/Genentech and Regeneron for INO-5401 (in bladder cancer and GBM), each providing for clinical evaluation of Inovio immunotherapies combined with checkpoint inhibitors. In particular, the INO-5401 collaborations are based on a strong scientific rationale to combine two immunotherapies: INO-5401, which generates antigen-specific killer T cells, and a checkpoint inhibitor, which augments T cell activity.

About Glioblastoma

Glioblastoma (GBM) is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, despite a limited number of new therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the average five-year survival rate is less than five percent.

About INO-5401

INO-5401 includes Inovio’s SynCon antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens are known to be over-expressed, and often mutated, in a variety of human cancers, and targeting these antigens may prove efficacious in the treatment of patients with cancer.

On April 1, 2019 AstraZeneca and MSD, Inc., Kenilworth, NJ, US (MSD: known as Merck & Co., Inc. inside the US and Canada) reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for the MEK 1/2 inhibitor and potential new medicine selumetinib (Press release, AstraZeneca, APR 1, 2019, View Source [SID1234534817]).

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This designation is for the treatment of paediatric patients aged three years and older with neurofibromatosis type 1 (NF1) symptomatic and/or progressive, inoperable plexiform neurofibromas (PN), a rare, incurable genetic condition.

José Baselga, Executive Vice President, Research and Development, Oncology, said: "Selumetinib shows promise in the treatment of NF1-related plexiform neurofibromas, a rare and debilitating disease with no approved medications to date. The Breakthrough Therapy Designation acknowledges the significant unmet need of these patients and the potential benefit of selumetinib in this setting."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, at MSD Research Laboratories, said: "This new designation validates our ongoing development of selumetinib. As a result of this, selumetinib has the potential to receive expedited regulatory review and we hope to bring this medicine to patients as soon as possible."

The BTD is based on Phase II data from the SPRINT trial, testing selumetinib as an oral monotherapy in paediatric patients, aged three years or older with inoperable NF1-related PN. The results of the trial were presented by the National Cancer Institute (NCI) at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

This is the ninth BTD that AstraZeneca has received from the FDA since 2014. BTD is designed to expedite the development and regulatory review of medicines that are intended to treat a serious condition and that have shown encouraging early clinical results, which may demonstrate substantial improvement on a clinically-significant endpoint over available medicines.

Selumetinib was granted Orphan Drug Designation for the treatment of NF1 by the US FDA in February 2018 and the European Medicines Agency in August 2018.

Selumetinib is a MEK 1/2 inhibitor and potential new medicine licensed by AstraZeneca from Array BioPharma Inc. in 2003. AstraZeneca and MSD entered a co-development and co-commercialisation agreement for selumetinib in 2017.

The NF1 gene provides instructions for making a protein called neurofibromin, which negatively regulates the RAS/MAPK pathway, helping to control cell growth, differentiation and survival. Mutations in the NF1 gene may result in dysregulations in RAS/RAF/MEK/ERK signalling, which can cause cells to grow, divide and copy themselves in an uncontrolled manner, and may result in tumour growth. Selumetinib inhibits the MEK enzyme in this pathway, potentially leading to inhibition of tumour growth.

Selumetinib is being assessed as a monotherapy and in combination with other treatments in ongoing trials.

About SPRINT

The SPRINT trial is a US Cancer Therapy Evaluation Program (CTEP) NCI-sponsored Phase I/II trial. The Phase I trial was designed to identify the optimal Phase II dosing regimen, and the results were published in the New England Journal of Medicine.1

About NF1

Neurofibromatosis type 1 (NF1) is an incurable genetic condition that affects one in 3,000 to 4,000 individuals.2,3 It is caused by a spontaneous or inherited mutation in the NF1 gene and is associated with many symptoms, including soft lumps on and under the skin (cutaneous neurofibromas), skin pigmentation (so-called ‘cafe au lait’ spots) and, in 20-50% of patients, tumours develop on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause clinical issues such as pain, motor dysfunction, airway dysfunction, bowel/bladder dysfunction and disfigurement as well as having the potential to transform into malignant peripheral nerve sheath tumours (MPNST).

People with NF1 may experience a number of complications such as learning difficulties, visual impairment, twisting and curvature of the spine, high blood pressure, and epilepsy. NF1 also increases a person’s risk of developing other cancers, including malignant brain tumours, MPNST and leukaemia. Symptoms begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.4

About the AstraZeneca and MSD Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza (olaparib), the world’s first PARP inhibitor and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On April 1, 2019 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported that the company will present at the H.C. Wainwright Global Life Sciences Conference in London on Monday, April 8, 2019 at 4:30 a.m. ET and the Needham Healthcare Conference in New York on Tuesday, April 9, 2019 at 2:50 p.m. ET (Press release, BioCryst Pharmaceuticals, APR 1, 2019, View Source [SID1234534816]).

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Links to a live audio webcast and replay of these presentations may be accessed in the Investors section of BioCryst’s website at http://www.biocryst.com.