On January 27, 2020 ORIC Pharmaceuticals, a privately held, clinical-stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported dosing of the first patient in a Phase 1b clinical trial being conducted under a collaboration with Astellas Pharma Inc., to evaluate the combination of ORIC-101, ORIC’s investigational glucocorticoid receptor (GR) antagonist, with XTANDI (enzalutamide) as a treatment for patients with metastatic prostate cancer that is progressing on enzalutamide (Press release, ORIC Pharmaceuticals, JAN 27, 2020, View Source [SID1234553596]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Research conducted by ORIC’s co-founder Charles Sawyers, MD, published in Cell, has elucidated that increased expression of GR in prostate cancer is associated with resistance to enzalutamide therapy. Furthermore, preclinical data generated by ORIC demonstrated that inhibition of GR signaling by ORIC‑101 can re-sensitize treatment-resistant prostate cancer models to enzalutamide.

"Enrollment of the first patient in this Phase 1b clinical trial of ORIC-101 marks the second clinical trial for this program and another major milestone for ORIC," said Jacob M. Chacko, MD, Chief Executive Officer. "Just as the glucocorticoid receptor has been linked to treatment resistance for multiple classes of chemotherapeutics across a variety of solid tumors, there are also strong scientific rationale and preclinical evidence supporting its linkage to prostate cancer resistance. We are delighted to collaborate with Astellas on this important study assessing the potential of ORIC-101 to benefit patients with metastatic prostate cancer that has progressed on enzalutamide, for which there are limited treatment options today."

The Phase 1b trial is a multi-center, open label, dose finding study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ORIC-101 combined with enzalutamide when administered to patients with metastatic prostate cancer that has progressed on enzalutamide. Once the recommended Phase 2 dose of ORIC-101 in combination with enzalutamide has been identified, the study will enroll patients into expansion cohorts based upon GR expression using ORIC’s proprietary immunohistochemistry assay.

"Despite the introduction of novel antiandrogen therapies for the treatment of prostate cancer, such as enzalutamide, the majority of responsive patients will ultimately become treatment resistant, resulting in poor prognoses for men diagnosed with this devastating condition," said Pratik S. Multani, MD, Chief Medical Officer. "We are excited to evaluate the therapeutic potential of ORIC-101 to overcome what we believe may be a key mechanism of resistance to antiandrogen therapy."

Under the terms of the clinical trial collaboration and supply agreement with Astellas, ORIC is sponsoring and conducting the Phase 1b study of ORIC-101 in combination with enzalutamide. Astellas, which commercializes XTANDI in the United States with Pfizer Inc, is providing enzalutamide for the study. ORIC maintains global development and commercial rights to ORIC-101 and rights to develop the program in combination with other agents.

Further details about the clinical study are available at ClinicalTrials.gov (NCT04033328).

About Metastatic Prostate Cancer

In the United States, prostate cancer is the second most prevalent cancer in men and the second leading cause of cancer death in men. The American Cancer Society estimates there are approximately 175,000 new cases of prostate cancer and over 30,000 deaths from the disease in the U.S. annually.

In men with prostate cancer, the disease is considered metastatic once the cancer has spread outside of the prostate gland to other parts of the body, such as the bones, lymph nodes, bladder and rectum. Men are considered hormone (or castration) sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels. Men are considered castration-resistant if their disease progresses despite androgen deprivation therapy and is often correlated with rising levels of prostate-specific antigen. Over 50,000 men are estimated to develop metastatic prostate cancer in the U.S. annually.

On January 27, 2020 On Target Laboratories, Inc., a privately-held biotechnology company developing the use of fluorescent markers to target and illuminate cancer during surgery, reported the results of a multi-institutional Phase 2 clinical trial in which outcomes were improved for 26 percent of patients undergoing pulmonary resection for non-small cell lung cancer (NSCLC) (Press release, Applied BioMath, JAN 27, 2020, View Source [SID1234553595]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The results were presented today at the 56th Annual Meeting of the Society of Thoracic Surgeons (STS), held in New Orleans, LA., and were featured in a plenary session as a J. Maxwell Chamberlain Memorial Paper for General Thoracic Surgery, considered to be among the top-rated abstracts at STS.

"Our goal is to provide surgeons with new technology to help them provide a more complete resection to more patients. This gives patients the best chance of improved outcomes after surgery," said Christopher Barys, president and CEO of On Target Laboratories.

Lung cancer is the leading cause of cancer-related deaths in the United States. Pulmonary resection, either a wedge resection, segmentectomy, or lobectomy, is recommended for most patients who have operable stage I-II non-small cell lung cancer. Intraoperative molecular imaging (IMI)—also referred to as fluorescence-guided surgery—may increase the likelihood of a more complete surgical resection, which could translate into increased survival for patients and reduced re-operations or adjuvant treatment for hospitals.

Conducted over 18 months, the study included 92 patients eligible for analysis. There were no drug-related serious adverse events and 24 patients (26 percent) were impacted during pulmonary resection, with eight percent of patients having a change in their stage due to the use of IMI.

The study showed that IMI improved localization of small and peripheral lesions, which can be difficult for surgeons to identify visually or through manual palpitation, and enabled localization of otherwise unlocalizable lesions in 11 patients (12%). Further ten additional cancers were found in seven patients (8%). During the Specimen Check Phase, when the surgeon confirms the nodule is in the specimen and analyzes the margins, surgeons felt all margins were adequate, yet back-table inspection using IMI revealed inadequate margins in eight patients (9%).

"OTL38 is the first technique that is specific to imaging adenocarcinomas of the lung, which is one of the most common types of invasive lung cancer," said Inderpal (Netu) S. Sarkaria, MD, Department of Cardiothoracic Surgery at the University of Pittsburgh Medical Center in Pennsylvania. "Near-infrared imaging with OTL38 may be a powerful tool to help surgeons significantly improve the quality of lung cancer surgery by more clearly identifying tumors and allowing the surgeon to better see and completely remove them—one of the most vital components in the overall care of patients with this disease."

OTL38 is under development in two Phase 3 clinical trials for lung and ovarian cancer indications. Both trials are being conducted under a Special Protocol Agreement with the FDA. OTL38 has also received a Fast Track designation for both the lung and ovarian cancer indications and an orphan designation for ovarian cancer from the FDA.

About Intraoperative Molecular Imaging

To date, there have been limited ways for surgeons to confidently assess the location and full extent of cancerous tissue while operating. On Target Laboratories’ fluorescent markers are comprised of a near-infrared dye and a targeting molecule, or ligand, that binds to receptors overexpressed on cancer cells. These markers illuminate the cancerous lesions, lighting the way for the resection of malignant tissue and enabling surgeons to see and remove more diseased tissue.

On Target’s first novel compound, OTL38, targets folate receptors commonly found on many cancers, including lung and ovarian cancers. A small single dose of the compound is administered via IV infusion one to 24 hours before surgery, allowing the surgeon to identify malignant tissue during the procedure using the near-infrared camera.

On January 27, 2020 Amgen (NASDAQ:AMGN) reported that it will report its fourth quarter and full year 2019 financial results on Thursday, Jan. 30, 2020, after the close of the U.S. financial markets (Press release, Amgen, JAN 27, 2020, View Source [SID1234553594]). The announcement will be followed by a conference call with the investment community at 2 p.m. PT. Participating in the call from Amgen will be Robert A. Bradway, chairman and chief executive officer, and other members of Amgen’s senior management team.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Live audio of the conference call will be simultaneously broadcast over the internet and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On January 27, 2020 Human Longevity, Inc. (HLI), an innovator in providing data-driven health intelligence and precision health to physicians and patients, reported the publication of a groundbreaking study in the journal Proceedings of the National Academy of Sciences (PNAS) (Press release, Human Longevity, JAN 27, 2020, View Source [SID1234553593]). The study titled, "Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging," showed that by integrating whole-genome sequencing with advanced imaging and blood metabolites, clinicians identified adults at risk for key health conditions. Data from 1190 self-referred individuals evaluated with HLI’s multi-modal precision health platform, Health Nucleus, show clinically significant findings associated with age-related chronic conditions including cancer, heart disease, diabetes, chronic liver disease, and neurological disorders — leading causes of premature mortality in adults.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The goal of precision medicine is to provide a path to assist physicians in achieving disease prevention and implementing accurate treatment strategies," said C. Thomas Caskey, MD, FACP, FACMG, FRSC, chief medical officer for Human Longevity, Inc., lead author of the study, and a member of the National Academy of Sciences. "Our study showed that by employing a holistic and data-driven health assessment for each individual, we are able to achieve early disease detection in adults."

Study highlights include:

Approximately 1 in 6 adult individuals (17.3%) had at least one pathogenic genetic variant, and when integrated with deep phenotyping (imaging, blood test, etc.), 1 in 9 (11.9%) had genotype and phenotype associations, supporting the clinical diagnosis of a genetic disorder.
Additional highly actionable findings in this self-referred cohort, most of which were not previously known, include:
Insulin resistance and/or impaired glucose tolerance (34.2%)
Elevated liver fat (29.2%)
Cardiac structure or function abnormalities such as valvular disorders (16.2%)
Significant calcified coronary artery plaque (calcium score > 100) (11.4%)
Elevated liver iron (9.3%)
Cardiac arrhythmias such as atrial fibrillation (6.1%)
Cardiac conduction disorders (4.8%)
Early stage tumors, most malignant (1.7%)
A lack of phenotype and genotype associations were observed in 5.8% of individuals with pathogenic genetic variants, further suggesting that the identification of pathogenic genetic variant(s) by sequencing alone is not sufficient for a definitive diagnosis, highlighting the importance of a multi-modal assessment.
Genomics and metabolomics associations revealed 5.1% of heterozygous carriers with phenotype manifestations, affecting serum metabolite levels, suggesting that some genetic carriers may not be completely asymptomatic.
"This study shows that the definition of ‘healthy’ may not be what we think it is and depends upon a comprehensive health evaluation," said J. Craig Venter, PhD, founder, Human Longevity, Inc. and a member of the National Academy of Sciences. "The data underscore Human Longevity’s innovative approach to helping clinicians with early detection and personalized treatments, potentially achieving better health outcomes for patients."

"Our traditional approach to the annual health assessment has been very superficial and will need to be replaced by data-driven measures that will be made possible as costs continue to decline for whole-genome sequencing, advanced imaging, especially MRI, and specialized blood analytics," said David Karow, MD, PhD, president and chief innovation officer, Human Longevity, Inc.

ABOUT THE STUDY

The study cohort was composed of 1190 self-referred participants who enrolled at Health Nucleus with a median age of 54 y (range 20 to 89+ y, 33.8% female, 70.6% European). A multidisciplinary team, including cardiologists, radiologists, primary care physicians, clinical geneticists, genetic counselors, and research scientists, integrated deep phenotype data with genome data for each study participant. Participants were enrolled in the study between September 2015 and March 2018.

On January 27, 2020 OncoImmune, Inc. reported that clinical data from its Phase IIa clinical trial of CD24Fc are being presented at the 2020 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR Meeting, taking place in Orlando, Florida in February (Press release, ONCOIMMUNE, JAN 27, 2020, View Source [SID1234553592]). The Phase IIa data will be presented by the study’s Principle Investigator, Dr. John Magenau of the University of Michigan’s Department of Medicine, at 11:15 am on February 21. Dr. Pan Zheng, the Chief Medical Officer of OncoImmune, Inc., will present Phase III clinical trial design in a poster session on February 19-20th.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CD24Fc is OncoImmune’s first-in class fusion protein that selectively represses inflammation induced by tissue injury while preserving innate immune response to pathogens. The Phase IIa study is a randomized, double blind, placebo controlled, multi-center study to investigate adding CD24Fc to standard of care tacrolimus and methotrexate in acute graft-versus host disease (GVHD) prophylaxis for allogeneic hematopoietic stem cell transplantation (HCT) with matched unrelated donors in treatment of leukemia and myelodysplastic syndrome. The trial included three CD24Fc dose cohorts: 240 mg at day -1, 480 mg at day -1, and the multi-dose cohort of 480-240-240 mg at day -1, day 14 and day 28. CD24Fc has received orphan drug designation from both the US FDA and European Medical Agency (EMA) for GVHD prophylaxis.

The presentation, entitled, "Mitigating Damage Response with CD24 Fusion Protein for Prevention of Acute Graft-Versus Host Disease," compares safety and efficacy data of CD24Fc when used in combination with standard of care GVHD prophylaxis compared to placebo and historical controls. The results demonstrate that CD24Fc was safe and well tolerated in the patient population. More importantly, patients receiving CD24Fc performed significantly better than placebo and historical controls in 180 day grade III-IV GVHD-free survival, the planned primary endpoint for the Phase III trial. These data thus provided strong support for the primary endpoint and dosing regimen of the upcoming phase III clinical trial. Moreover, significantly better relapse free survival (RFS) was observed over placebo control and historical controls. Overall survival (OS) was also significantly improved when compared with a matched historical control. Furthermore, a significant, dose-dependent reduction of mucositis was observed.

"We are very excited by the data observed in the Phase IIa clinical trial. In addition, we have completed enrollment of an open label Phase II expansion study where the drug continues to perform very well with clear signs of clinical efficacy," said Dr. Pan Zheng. "HCT is a curative therapy for refractory leukemia patients but hampered by GVHD, leukemia relapse and conditioning toxicity. As suggested by our preliminary data, CD24Fc shows significant promise in all three of these outcomes and would likely be transformative for the HCT field," she continued.