On February 6, 2019 Pathios Therapeutics ("Pathios"), an innovative biotech company focused on the development of first in class therapies for autoimmune diseases and immuno-oncology and Sygnature Discovery ("Sygnature"), reported a strategic partnership to accelerate Pathios’ drug discovery and development programmes (Press release, Pathios Therapeutics, FEB 6, 2019, View Source [SID1234650160]).

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As part of the agreement, Pathios and Sygnature will collaborate on an integrated drug discovery programme against a novel G Protein-Coupled Receptor (GPCR) target. Specifically, Sygnature are providing their industry leading expertise in GPCR bioscience and medicinal chemistry to expand Pathios’ current hit-to-lead programme. Sygnature are also deploying their computational chemistry, library design and synthesis and medium throughput screening capability to broaden Pathios’ hit finding. As part of this agreement, Sygnature will receive equity in addition to fees.

Pathios Therapeutics brings together cutting-edge European science and a leading drug discovery and development team to modulate the activity of GPR65, a pH sensing GPCR. This drug target is characteristic of certain T helper 17 (Th17) cell populations which have been shown to contribute significantly to the pathology of autoimmune conditions, such as ankylosing spondylitis and psoriatic arthritis. In addition, recently published studies have demonstrated GPR65 drives tumour associated macrophages (TAM) to adopt a phenotype that supports cancer immune evasion.

Tom McCarthy, Executive Chairman and Co-founder of Pathios Therapeutics Limited, commented: "We founded Pathios to build on emerging science that demonstrated GPR65 sits at the nexus of autoimmune disease and immuno-oncology as this receptor links pathology caused by a low pH environment. The ultimate aim is to block the pathological process that GPR65 initiates without interfering with the physiological role of this receptor. In addition to developing potent and selective drugs to modulate GPR65, we are continuing to broaden the understanding of the fundamental biological processes that link to GPR65’s effects in Th17 cells, TAMs and other cell types. Our team has worked closely with Sygnature in the past and know they have the deep experience, expertise and state-of-the-art drug discovery and development infrastructure to drive our programme forward. I’m delighted on this rare occasion Sygnature also chose to invest in Pathios and expand our GPR65 drug discovery efforts while we explore Series A funding opportunities".

Simon Hirst, CEO of Sygnature, added: "We are extremely pleased to take this exceptional opportunity to partner with, and invest in Pathios on their drug discovery projects. Based on our diligence activities, we are excited about the potential for GPR65 modulation to be central to new treatments for autoimmune disease and a critical mechanism of action in next generation immunooncology drugs targeting the tumour micro-environment. We are excited to have the opportunity to work with Tom and the rest of Pathios’ tremendously talented team again and contribute to the potential positive impact their therapeutics will have on patients’ lives".

On February 6, 2019 Cofactor Genomics, pioneers in the field of Predictive Immune Modeling, reported a $100,000 grant program to reward innovations with the Cofactor ImmunoPrismTM Assay (Press release, Cofactor Genomics, FEB 6, 2019, View Source [SID1234533097]). The program was unveiled at the 2019 Immuno-Oncology 360° Conference in New York.

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In December 2018, Cofactor made available the use of its proprietary database of Health Expression Models (HEMs). The Health Expression Models leveraged in the ImmunoPrism Assay enable quantification of immune cells and subtypes in solid tumor tissue, shown to be important in predicting response to immunotherapies. Built using machine-learning, these models have been demonstrated to provide measurable improvements to sensitivity and specificity over single-gene approaches currently used by the field. Access to Cofactor’s database of Health Expression Models has empowered translational and clinical scientists, along with drug development companies to utilize multidimensional biomarkers in their cancer research and clinical trials. Early adopters of Cofactor’s Predictive Immune Modeling technologies include the Fred Hutchinson Cancer Research Center, National Cancer Institute, and Genocea Biosciences.

"We are sitting on the 10 year anniversary of RNA-seq with shelves stuffed full of samples and data, created by cell profiling and analysis, yet we still can’t answer the fundamental question of predicting which immunotherapy will work with a specific patient or certain type of cancer," said Jarret Glasscock, Cofactor CEO and founder. "The new Predictive Immune Modeling Grant is designed to inspire the science, research, and clinical communities to take a different approach to producing highly predictive multidimensional biomarkers to ultimately solve this massive problem."

Cofactor Genomics will be showcasing its Predictive Immune Modeling technology during the Immuno-Oncology 360 conference with a talk in the "Transactional Science & Emerging Biomarkers" track and the panel on "Next Generation Biomarker and Companion Diagnostics for Predicting Response."

Applications for the Grant Program will be accepted through April 15, 2019 and more details may be found here: View Source

On February 6, 2019 Blue Earth Diagnostics, a molecular imaging diagnostics company, reported the upcoming presentation of additional analyses from the LOCATE clinical trial (NCT02680041) (Press release, Blue Earth Diagnostics, FEB 6, 2019, View Source [SID1234533098]). The LOCATE trial is a prospective, U.S., multicenter, open-label study investigating the impact of 18F fluciclovine PET/CT imaging on patient management of biochemically recurrent prostate cancer after initial prostate cancer treatment and negative or equivocal findings on standard-of-care imaging. The presentation will be made at the ASCO (Free ASCO Whitepaper) 2019 Genitourinary Cancers Symposium (ASCO GU), from February 14-16, 2019 in San Francisco, Ca. Details of the presentation to be given by Blue Earth Diagnostics collaborators is listed below.

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Date: Thursday, February 14, 2019
Presentation: Identification of bone involvement in patients with prostate cancer recurrence using 18F-fluciclovine PET/CT and impact on subsequent management
Abstract Number: 248

Presenter: Michael S Kipper, MD, Genesis Healthcare, on behalf of the LOCATE study group
Session Title & Times: Poster Session A: Prostate Cancer
11:30 AM-1:00 PM and 5:30 PM-6:30 PM PT
Location: Moscone West Building, San Francisco, Ca.

Blue Earth Diagnostics invites participants at the ASCO (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium 2019 to attend the above presentation and to learn more about the company at Exhibit 36.

U.S. Indication and Important Safety Information About Axumin

INDICATION

Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full Axumin prescribing information is available at www.axumin.com.

About Axumin (fluciclovine F 18)

Axumin (fluciclovine F 18) injection is a novel product indicated for use in positron emission tomography (PET) imaging to identify suspected sites of prostate cancer recurrence in men. Recurrence of prostate cancer is suspected by an increase in prostate specific antigen (PSA) levels following prior treatment. PET imaging with Axumin may identify the location and extent of such recurrence. Axumin was developed to enable visualization of the increased amino acid transport that occurs in many cancers, including prostate cancer. It consists of a synthetic amino acid that is preferentially taken up by prostate cancer cells compared with surrounding normal tissues, and is labeled with the radioisotope F 18 for PET imaging. Fluciclovine F 18 was invented at Emory University in Atlanta, Ga., with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences. Axumin was approved by the U.S. Food and Drug Administration in May 2016, following Priority Review, and is the first product commercialized by Blue Earth Diagnostics, which licensed the product from GE Healthcare. The molecule is being investigated by Blue Earth Diagnostics for other potential cancer indications, such as glioma.

On February 6, 2019 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported the presentation of updated biomarker and clinical results from its two lead programs that target the adenosine pathway, CPI-444, an adenosine A2A receptor antagonist, and CPI-006, an anti-CD73 antibody (Press release, Corvus Pharmaceuticals, FEB 6, 2019, View Source [SID1234533117]). The data were presented by Stephen Willingham, Ph.D., Senior Scientist at Corvus, at the Immuno-Oncology 360° Conference in New York during the "Discovery & Preclinical Science Plenary" session, which focused on tumor microenvironment changing technologies, pegylated cytokines and additional discovery and preclinical data.

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Key CPI-444 Biomarker Results
Dr. Willingham’s presentation, titled "Blockade of the Adenosine Pathway: Preclinical, Translational and Clinical Studies with CPI-444, an A2A Receptor Antagonist for Cancer Treatment," reviewed gene expression data of an adenosine gene signature recently announced by Corvus (or AdenoSig), in patients with renal cell carcinoma (RCC) who are participating in Corvus’ ongoing Phase 1/1b study of CPI-444, a selective and potent inhibitor of the adenosine A2A receptor. In particular, the data from the study showed a relationship of this novel biomarker to angiogenesis gene expression data (or angiogenesis signature). Such findings indicate that expression of AdenoSig was inversely related to the angiogenesis signature, which has been well studied by others and correlates with response to vascular endothelial growth factor receptor (VEGFR) inhibitors such as Sutent (sunitib malate) and other tyrosine kinase inhibitors. Low expression of angiogenesis genes predicts a lack of response to VEGFR inhibition. These data suggest that patients with a high AdenoSig are potentially more likely to respond to treatment with CPI-444 and less likely to respond to VEGFR inhibitors.

"Based on these translational data, we expect that we may be able to use the AdenoSig as a predictive biomarker to identify patients for adenosine pathway inhibition and select patients for future trials of CPI-444," said Dr. Willingham. "The gene expression data also may enable us to select the optimum patients for combination therapy with CPI-006, our anti-CD73 antibody, which has demonstrated unique immunologic activity in early clinical trials."

Key CPI-006 Clinical Results
Dr. Willingham also presented updated clinical results from the ongoing Phase 1/1b dose-escalation study of CPI-006 in patients with a variety of advanced cancers, including non-small cell lung cancer (NSCLC), RCC and other cancers who have failed standard therapies. The first arm of the study is evaluating CPI-006 as a monotherapy, a second arm is evaluating CPI-006 in combination with CPI-444, and a third arm is planned to evaluate CPI-006 in combination with pembrolizumab, an anti-PD-1 antibody. In particular, the updated results demonstrated that:

CPI-006 given as a monotherapy activated B cells and led to a redistribution of these cells along with changes in other immune cells (e.g., changes in T helper to T suppressor ratios). These data are consistent with immune stimulation induced by CPI-006.
CPI-006 reacted with an epitope on CD73 that led to blockade of adenosine production and expression of lymphocyte activation antigens that are independent of adenosine.
"We continue to advance our two lead therapeutic programs that target the adenosine-cancer pathway. We believe we are well positioned for a potential pivotal trial of CPI-444 in renal cell carcinoma and other tumors based on the biomarker signature we discovered, and CPI-006 is beginning to show early signs of immunologic activity that may be important in cancer therapy," said Richard A. Miller, M.D., an oncologist and co-founder, president and chief executive officer of Corvus. "Regarding our third pipeline program, we anticipate starting a Phase 1/1b trial of CPI-818, an ITK inhibitor for T-cell lymphoma, during the first quarter of 2019."

About CD73 and Adenosine
CD73 is a cell surface enzyme whose function is to convert adenosine monophosphate (AMP) to adenosine by removing phosphate from AMP. CD73 is expressed on cells of the immune system, including T-cells and B-cells. CD73 is also present on many tumors, including lung, renal, melanoma, colon, prostate, breast and others. In the tumor microenvironment, CD73 produces adenosine, which binds to the adenosine A2A receptor on immune cells and inhibits various immune responses including those directed against the tumor. Tumors utilize this immunosuppressive mechanism to escape attack by the immune system.

About CPI-006
CPI-006 is a potent humanized monoclonal antibody that reacts with the active site of CD73, blocking the conversion of AMP to adenosine. In vitro studies of CPI-006 have shown it is capable of substantially inhibiting the production of adenosine by blocking the CD73 enzyme and leads to activation of peripheral blood B cells.

About CPI-444
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic.

On February 5, 2019 Sanofi reported that the pivotal Phase 3 trial of isatuximab in patients with relapsed/refractory multiple myeloma met the primary endpoint of prolonging progression free survival in patients treated with isatuximab in combination with pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone alone (standard of care) (Press release, Sanofi, FEB 5, 2019, View Source [SID1234533065]).

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Results will be submitted to an upcoming medical meeting and are anticipated to form the basis of regulatory submissions planned for later this year.

"We are excited by these results, which represent significant progress in our ambition to extend the lives of multiple myeloma patients," said John Reed, Head of Research and Development at Sanofi. "We look forward to engaging with regulatory authorities with the goal of bringing this potential new treatment to patients as quickly as possible."

Multiple myeloma is the second most common hematologic malignancy[1], with more than 138,0002 new cases worldwide each year. Multiple myeloma remains incurable in the vast majority of patients, resulting in significant disease burden.

The randomized, multi-center, open label Phase 3 study, known as ICARIA-MM, enrolled 307 patients with relapsed/refractory multiple myeloma across 96 centers spanning 24 countries. All study participants received two or more prior anti-myeloma therapies, including at least two consecutive cycles of lenalidomide and a proteasome inhibitor given alone or in combination. During the trial, isatuximab was administered through an intravenous infusion at a dose of 10mg/kg once weekly for four weeks, then every other week for 28-day cycles in combination with standard doses of pomalidomide and dexamethasone for the duration of treatment. The safety profile was evaluated as a secondary endpoint.

About isatuximab clinical development program

Isatuximab targets a specific epitope of CD38 capable of triggering multiple, distinct mechanisms of action that are believed to promote programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and is a cell surface receptor target for antibody-based therapeutics in multiple myeloma and other malignancies. The clinical significance of these findings is under investigation.

ICARIA-MM is one of four ongoing Phase 3 clinical trials evaluating isatuximab in combination with currently available standard treatments for people with relapsed/refractory or newly-diagnosed multiple myeloma.

Isatuximab received orphan designation for relapsed/refractory multiple myeloma by the U.S. Food and Drug Administration and the European Medicines Agency. Isatuximab is an investigational agent and the safety and efficacy has not been evaluated by the U.S. Food and Drug Administration, the European Medicines Agency, or any other regulatory authority. Isatuximab is also under investigation for the treatment of other hematologic malignancies and solid tumors.