On March 25, 2019 BioXcel Therapeutics, Inc. ("BTI") (BTAI) reported that it has filed a Clinical Trial Application (CTA) with the U.K. health authorities for its lead immuno-oncology asset, BXCL701, an orally-available small molecule immune-modulator with dual mechanisms of action, in combination with pembrolizumab (Keytruda), a checkpoint inhibitor, in tNEPC (Press release, BioXcel Therapeutics, MAR 25, 2019, View Source [SID1234534627]). BTI is a clinical-stage biopharmaceutical development company utilizing novel artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology.

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Following approval of the CTA, BTI plans to expand the Phase 1b/2 US study of BXCL701 and pembrolizumab in tNEPC to the U.K. Professor Johann de Bono, M.D., Ph.D., of The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, will serve as Principal Investigator for the European study of BXCL701 in tNEPC. Data from the open-label trial will support the ongoing global clinical development of BXCL701.

Additionally, BioXcel Therapeutics is preparing to file an Investigational New Drug (IND) application with the FDA for a clinical trial evaluating the triple combination of BXCL701, NKTR-214 and avelumab in the treatment of advanced pancreatic cancer.

Dr. Chetan D. Lathia, SVP & Head of Translational Medicine, Clinical Pharmacology and Regulatory Affairs of BTI said, "The filing of the CTA in the U.K., for the BXCL701 combination trial is an important regulatory milestone for BTI. It marks the beginning of our plans for the global development of our lead programs."

Dr. Vimal Mehta, Chief Executive Officer of BTI added, "We remain committed to translating the potential of BXCL701’s novel mechanism of action into therapies that can fundamentally change the lives of cancer patients. The filing of this CTA is the first milestone in the expansion of our footprint into major markets outside the US. We believe that our pancreatic cancer clinical development partnership with Nektar, Pfizer and Merck KGaA, Darmstadt, Germany will also benefit the broader BXCL701 program."

The Company also announced that Professor de Bono has joined its Immuno-oncology Clinical Advisory Board. Professor De Bono is the Regius Professor of Cancer Research and a Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. He is also the Director of the Drug Development Unit, overseeing the Phase I trials, with a particular interest in innovative trial designs, circulating biomarkers and prostate cancer. Additionally, he leads the Prostate Cancer Targeted Therapy Group and the Cancer Biomarkers laboratory team. He has served as chief investigator on trials for multiple approved drugs, including ZYTIGA, JEVTANA and XTANDI.

Professor de Bono is a clinical investigator in the KEYNOTE- 199 trial, a study evaluating Pembrolizumab in docetaxel pre-treated castrate-resistant metastatic prostate cancer patients. He graduated with a medical degree and a postdoctoral degree from University of Glasgow. He also trained in medical oncology and was awarded a master’s degree in cancer sciences from the University of Glasgow. Professor de Bono has received multiple awards including one of the "World’s Most Influential Scientific Minds," the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) award and the Royal Society of Chemistry award.

About BXCL701

BXCL701 is an orally-available systemic innate-immune activator with dual mechanisms of action. It has demonstrated single agent activity in melanoma, with an established safety profile from 700 healthy subjects and cancer patients. Designed to stimulate both the innate and acquired immune systems, BXCL701 works by inhibiting dipeptidyl peptidase (DPP) 8/9 and blocking immune evasion by targeting Fibroblast Activation Protein (FAP). Preclinical combination data evaluating BXCL701, a checkpoint inhibitor and other immuno-oncology agents has demonstrated encouraging anti-tumor activity in multiple tumor types and formation of functional immunological memory. BXCL701’s primary mechanism of action has recently been highlighted in multiple peer reviewed journals, providing an important validation of the scientific rationale behind BXCL701.

On March 25, 2019 Pain Therapeutics, Inc. (Nasdaq: PTIE) reported financial results for the year ended December 31, 2018 (Press release, Pain Therapeutics, MAR 25, 2019, View Source [SID1234534594]). Net loss in 2018 was $6.6 million, or $0.61 per share, compared to a net loss in 2017 of $11.9 million, or $1.82 per share. Cash used in operations during the year ended December 31, 2018 was $4.8 million. Cash and cash equivalents were $19.8 million as of December 31, 2018, with no debt. We believe net cash utilization in 2019 will be in the range of $5.0 – $6.0 million.

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Historically, our focus was on analgesic drug development. In 2019, however, we will rebrand around neurodegenerative diseases, such as Alzheimer’s disease. Our rebranding plans include a new company name, logo, ticker symbol and website, as well as a comprehensive strategy to bolster media outreach and an active approach to engage with potential new shareholders.

"There’s never been a more exciting time to be in Alzheimer’s research," said Remi Barbier, President & CEO. "For many years, the prevailing scientific hypothesis said amyloid must be cleared out of the brain. This hypothesis has been tested in clinical studies using a variety of antibody backbones, epitopes, target conformations, biomarkers and in various stages of disease. These amyloid-clearing studies have one thing in common: they’ve all failed. It’s now prudent to consider more recent scientific breakthroughs in Alzheimer’s research. We think these are the innovations that stand a chance of making a difference for patients with Alzheimer’s disease."

Overview of Alzheimer’s Program
Over the past ten years, we have developed a new and highly promising scientific approach for the treatment and detection of Alzheimer’s disease. Importantly, our science does not seek to clear amyloid from the brain. Our approach is to stabilize a critical protein in the brain.

Starting with basic research, we have identified a structurally altered protein in the brain, also called a ‘proteopathy’. This proteopathy plays a critical role in the neurodegeneration observed in Alzheimer’s disease. Using scientific insight and advanced tools in biochemistry, bioinformatics and imaging, we have elucidated this protein dysfunction. We engineered a family of high-affinity small molecules to target the structurally altered protein and to restore this protein to its normal shape and function. Our drug candidate, PTI-125, is a small molecule that targets an altered form of a scaffolding protein called filamin A (FLNA). Study animals treated with PTI-125 showed significant improvements in neuronal function and decreases in neuroinflammation, resulting in cognitive improvement and slowing of disease progression.

In 2017, we successfully completed a Phase I clinical study with PTI-125. In 2018, we initiated a Phase IIa study with PTI-125 in patients with mild-to-moderate Alzheimer’s disease, with scientific and financial support from the National Institutes of Health (NIH). In 2019, we expect to conclude our Phase IIa study and announce clinical results.

We are also developing an experimental biomarker/diagnostic, called PTI-125Dx, to detect Alzheimer’s disease with a simple blood test. This program has financial support from the NIH.

The underlying science for our programs in neurodegeneration is published in several prestigious, peer-reviewed technical journals, including Journal of Neuroscience, Neurobiology of Aging, and Journal of Biological Chemistry.

In addition, in 2018 the National Institute on Aging of the NIH awarded our scientific programs two research grants. Collectively, these represent up to $6.7 million of non-dilutive financing.

Financial Highlights for 2018

At December 31, 2018, cash and cash equivalents were $19.8 million, compared to $10.5 million in 2017. We have no debt.
Net cash used in operations during the year ended December 31, 2018 was $4.8 million.
Research and development expenses for the year ended December 31, 2018 were $3.0 million compared to $7.6 million for the same period in 2017, or a 61% decrease. This was due primarily to decreases in analgesic drug development related expenses.
We received reimbursements of $3.0 million in 2018 from research grants from the NIH that we recorded as a reduction of research and development expense compared to $1.4 million in 2017.
Research and development expenses included non-cash stock related compensation costs of $1.0 million for the year ended December 31, 2018 and $1.2 million for the same period in 2017.
General and administrative expenses for the year ended December 31, 2018 were $3.7 million compared to $4.3 million for the same period in 2017, or a 15% decrease. This was due primarily to a decrease in non-cash stock-based compensation expenses as well as outside professional fees. General and administrative expenses included non-cash stock-based compensation costs of $1.4 million in the year ended December 31, 2018 and $1.8 million for the same period in 2017.
On August 17, 2018, we announced the closing of a registered direct offering of 8,860,778 shares of our common stock and issuance of warrants. Total net proceeds from the offering were approximately $10.2 million. In addition, we raised approximately $3.9 million of net proceeds through our At-The-Market common stock offerings during 2018.
In August and in October 2018, we announced that the NIH had awarded us research grants to support a Phase II program with PTI-125, our drug candidate to treat Alzheimer’s disease. Collectively, the NIH grants represent up to $6.7 million of non-dilutive financing.
Operating Highlights for 2018 and Forecast for 2019

Historically, our lead drug candidate had been REMOXY, which is the trade name for an abuse-deterrent, extended-release form of oxycodone to treat severe chronic pain. The U.S. Food and Drug Administration (FDA) has previously found REMOXY to be an effective analgesic drug for the treatment of severe chronic pain. However, FDA has not approved REMOXY on the basis that additional demonstrations of its abuse deterrent properties are needed, a matter of dispute between us and FDA.
On March 20, 2019, we provided Durect Corporation with written notice of termination of a Development and License Agreement (DLA). Termination of the DLA effectively ends our clinical development of REMOXY.

In October 2018, we announced a strategic reorganization to align Company resources on advancing our programs in neurodegenerative diseases, such as Alzheimer’s disease.

In December 2018, we announced the initiation of a Phase II study to evaluate PTI-125 in patients with Alzheimer’s disease. This clinical study is supported by a research grant award from the National Institute on Aging of the NIH, the primary Federal agency supporting innovative new research in Alzheimer’s disease.

In 2019, we expect to rebrand the Company around neurodegeneration. Our rebranding plans include a new company name, logo, ticker symbol, website, as well as a comprehensive strategy to bolster media outreach and an active approach to engage with potential new shareholders.
About Alzheimer’s Disease
Alzheimer’s disease is a progressive brain disorder that destroys memory and thinking skills. Eventually, a person with Alzheimer’s disease may be unable to carry out even simple tasks. Currently, there are no drug therapies to halt Alzheimer’s disease, much less reverse its course. Alzheimer’s disease is likely to become one of the world’s most serious future health care crisis.

On March 25, 2019 CIRCULOGENE, advancing precision medicine through personalized molecular genetics testing, reported that it will be presenting three abstracts at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, March 29 – April 3, 2019, at the Georgia World Congress Center in Atlanta (Press release, Circulogene, MAR 25, 2019, View Source [SID1234534610]). The poster sessions demonstrate CIRCULOGENE’s rapid, powerful and full-spectrum diagnostics capabilities using proprietary sample preparation coupled with next-generation sequencing (NGS) techniques to assess tumor mutation load at the patient level, even from low-yield, poor quality samples.

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The three posters accepted for presentation are:

Abstract No. 437 / 9: "Combining circulating stromal cells with cell free DNA for increased sensitivity in profiling oncogenic mutations and indicates highly aggressive non small cell lung cancer," investigating the clinical potential of CIRCULOGENE’s Patient Mutation Load (PML) analysis from matched cfDNA, cancer-associated macrophage-like cells (CAMLs), and tumor tissue to evaluate progression free survival (PFS) and overall survival (OS) in non-small-cell lung cancer (NSCLC).
March 31, 2019, 1:00 p.m. – 5:00 p.m. Section 18.
Presenter: Daniel L. Adams, Creatv MicroTech Inc., Monmouth Junction, NJ
Abstract No. 1368 / 7: "Simultaneous cell-free RNA PD-L1 expression and MSI from the same single-tube of blood in solid tumors" investigates the feasibility of simultaneous cfRNA PD-L1 and MSI testing from the same single tube of blood in a liquid biopsy.
April 1, 2019, 8:00 a.m. – 12:00 p.m. Section 19.
Presenter: Glen J. Weiss, M.D., MBA, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA
Abstract No. 4227 / 17: "Salvage genetic testing on buccal swab samples using liquid in situ amplification identifies genetic mutations from previous test failures" presents findings on the application of liquid in situ amplification (LISA) followed by hereditary testing on previously failed buccal swab samples to yield a genetic testing result.
April 2, 2019, 1:00 p.m. – 5:00 p.m. Section 28.
Presenter: Glen J. Weiss, M.D., MBA, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA.
CIRCULOGENE is one of very few liquid biopsy laboratories with preliminary data on the clinical application of cfDNA patient mutational load. Built upon its current 50-gene targeted panel and bioinformatics, CIRCULOGENE’s PML analysis showed promising prognostic value in terms of PFS and OS in NSCLC patients. CIRCULOGENE is looking forward to conducting further studies to unlock the full potential of the PML to improve patient care.

"We’re particularly excited about the potential for using cfDNA (in conjunction with CAMLs) for identification of highly aggressive forms of NSCLC with unfavorable prognosis," said CIRCULOGENE Chief Scientific Officer Chen-Hsiung Yeh, Ph.D. "This research uses our Personalized Gene Profile (CGP) 50-gene panel to determine PML from a single blood sample with increased sensitivity and specificity compared to tumor biopsy. CIRCULOGENE’s unique sample preparation technology was exclusively selected for this study. Given the rarity of CAMLs in the blood, the starting material usually has just a few to several hundred purified CAMLs."

All poster sessions take place in Exhibit Hall B. The full text of Regular Abstracts accepted for presentation are posted on the AACR (Free AACR Whitepaper) Online Itinerary Planner.

The highly accurate, automated and scalable cell-free DNA and RNA technology platform from CIRCULOGENE enables comprehensive genomic testing services. These capabilities help oncologists and pathologists select the right clinical trials and the most effective cancer therapies available for their patients, as well as monitoring patient responses, drug resistance, minimal residual disease and relapse.

CIRCULOGENE is the only company that provides circulating DNA, RNA (somatic and germline), and MSI cancer immunotherapy testing from a single tube of blood. Industry-leading turnaround times ensure that complete testing results are available to physicians and their patients within one week, all from a single 4 mL tube of blood, no matter which test or how many tests are ordered.

CIRCULOGENE is a Clinical Laboratory Improvement Amendments (CLIA) certified and College of American Pathologists (CAP) accredited laboratory and is registered as a verified U.S. federal contractor. For more information, visit our website, connect with us on LinkedIn, Facebook and Twitter, email us at [email protected] or call 855-614-7083. Clinicians interested in ordering tests may visit the Contact page on CIRCULOGENE’s website.

On March 25, 2019 Arch Oncology, Inc., a clinical-stage immuno-oncology company focused on the discovery and development of best-in-class anti-CD47 antibody therapies, reported a successful $50 million Series B financing (Press release, Arch Oncology, MAR 25, 2019, View Source [SID1234534595]). The Company plans to use the proceeds from this financing to advance its anti-CD47 antibody AO-176’s ongoing Phase 1 clinical trial in select solid tumors, as well as its pipeline.

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This financing included Arch Oncology’s existing investors, RiverVest Venture Partners, Roche Venture Fund, and 3×5 Partners, and was led by new investor Lightchain (Scottrade Founder and former CEO Rodger Riney’s family office).

"Our investors share our commitment to the exciting work we are doing to develop best-in-class antibodies aimed at improving treatment options for patients with cancer," said Julie M. Cherrington, Ph.D., President and Chief Executive Officer of Arch Oncology. "This financing supports our ongoing Phase 1 clinical trial for AO-176, our highly-differentiated anti-CD47 antibody, as we continue to dose patients. Additionally, these proceeds enable us to advance our discovery-stage pipeline. With the backing of our investors and the hard work of our experienced team, we look forward to developing new cancer treatment options for patients."

"Over the past year, the Arch Oncology team under Julie’s leadership has successfully executed on plans to advance AO-176 from the laboratory, through IND submission, and into the clinic," said John McKearn, Ph.D., Managing Director, RiverVest Venture Partners and Chairman of the Board of Arch Oncology. "We believe AO-176 has a best-in-class profile among agents in the anti-CD47 space and we are excited to see the progress advancing the pipeline."

On March 25, 2019 Onxeo SA (Euronext Paris, NASDAQ Copenhagen: ONXEO), (" Onxeo " or "the Company "), a clinical stage biotechnology company specializing in the development of innovative oncology drugs targeting tumor DNA damage response mechanisms (DDR), in particular to fight against rare or resistant cancers, reported that information on the five study presentations presenting important data on AsiDNA , its most advanced candidate, which will be presented in the form of posters in Congress American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting , March 29 – April 3, 2019, Atlanta, Georgia, United States (Press release, Onxeo, MAR 25, 2019, View Source [SID1234534611]).

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Françoise Bono, Scientific Director of Onxeo, says :"We are very pleased that these five studies have been accepted for presentation at the prestigious AACR (Free AACR Whitepaper) Conference. This recognition illustrates the interest, quality and diversity of translational research that we are currently conducting with AsiDNA . Our data once again demonstrate the singularity of our lead compound and its unique properties, particularly to prevent the emergence of treatment resistance, one of the most troubling issues in oncology today. All these data complement and reinforce our arguments for the further clinical development of AsiDNA , which is scheduled to begin in the coming weeks, now that we know the doses for which AsiDNA activates its cellular targets and confirmed its favorable safety profile, in the phase 1 study, DRIIV. We look forward to presenting the very promising results we have achieved and discussing them at this conference. "

Details of the sittings of April 1st and 2nd, 2019:

Abstract 2095 / Poster 2 – AsiDNA , a targeted treatment with no acquired resistance

Session: PO.ET03.03. Drug Resistance 3
Date: Monday 1 st April
Time: 1:00 p.m. to 5:00 p.m. AND
Location: Section 11

AsiDNA is the first antitumor drug in the field of DDR acting as an agonist 1. It causes a strong warning signal of the presence of DNA damage. This study demonstrates that long-term exposure of cancer cells to this warning signal does not promote the emergence of AsiDNA resistance. In contrast, repeated exposure downregulates the targeted repair pathways, a condition that persists for several months after AsiDNA treatment. This property is due to the singular mechanism of action of AsiDNA , which simulates a signal of DNA damage through over-activation (agonist effect) of the DNA-PK and PARP enzymes. This property is not observed with other DNA repair inhibitors such as PARP inhibitors olaparib and talazoparib which all eventually induce resistance. Long-term treatment with AsiDNA instead decreases the "vigilance" of the tumor cells, which improves the effectiveness of the product. These results indicate that agonist drugs such as AsiDNA may induce tumor cell evolution with a reduction in their ability to respond when signaling lesions on their DNA.

Abstract 2130/7 – Development of a biomarker-based patient selection strategy for AsiDNA treatment (collaboration with Institut Curie)

Session: PO.ET04.04 – Molecular Classification of Tumors
Date: Monday 1 st April
Time: 1:00 p.m. to 5:00 p.m.
Location: Section 12

_______________
1 Agonist: who has the property to activate

It remains very difficult to accurately assess and predict the response to cancer treatment. Stratification biomarkers are a valuable aid in identifying the patients most likely to respond to a particular drug, or even to distinguish between early and delayed responses. In this study, we identified a genetic signature that predicts the efficacy of AsiDNA treatment in patients. AsiDNA is currently in clinical trial and rapid validation of the most sensitive gene cluster is possible, with a view to developing a biomarker-based patient selection strategy for AsiDNA treatment.

Abstract 2918/6 – Molecular analysis of the mechanism of action of AsiDNA provides new clues to the regulation of DNA damage response

Session: PO.TB09.01 – Tumor Radiosensitivity or Resistance
Date: Tuesday, April 2
Time: 8:00 – 12:00
Location: Section 8

In this study, the different stages of AsiDNA activity were analyzed. The data show that AsiDNA inhibits the joining of non-homologous ends of DNA (NHEJ) and the repair of DNA double-strand breaks by homologous recombination by preventing the recruitment of key enzymes at the site of the break. Inhibition of recruitment of proteins involved in NHEJ is the first event and requires the activity of PARPs. Inhibition of homologous recombination proteins occurs late and depends on the activation of DNA-PK. PARP activation induces a metabolic change that could participate in the antitumor activity of AsiDNA .

Abstract 2865/6 – AsiDNA , a novel DNA repair inhibitor for sensitizing aggressive subtypes of medulloblastoma (Institut Curie)

Session: PO.TB09.01 – Targets and Therapies in Pediatric Cancer
Date: Tuesday, April 2
Time: 8:00 – 12:00
Location: Section 6

Medulloblastoma is a tumor of the cerebellum, and is the most common malignant brain tumor in children. There is often significant treatment-related mortality. It is therefore important to improve treatment efficacy for the most aggressive subgroups and to reduce treatment-related mortality for all subgroups. In this study, no increase in post-irradiation toxicity was observed with AsiDNA . In vivo, AsiDNA alone significantly improves survival rates (p = 0.005) and the effectiveness of radiotherapy. In combination with radiation therapy, AsiDNA can delay tumor growth and improve survival compared to radiotherapy alone.

Abstract 3797/2 – AsiDNA abrogates acquired resistance to PARP inhibitors

Session: PO.ET03.05 – Drug Resistance 5
Date: Tuesday, April 2
Time: 1:00 pm – 5:00 pm
Location: Section 10

PARP inhibitors (PARPi) are approved for the treatment of cancers with a deficient homologous recombination pathway. Despite the success of this approach, resistance to these drugs remains a clinical problem. In this study, long-term exposure of cancer cells to PARPi showed resistance in all independent populations tested, raising the question of the clinical benefits of long-term continuation of PARPi monotherapy. Interestingly, populations treated with AsiDNA (2.5 μM – low non-cytotoxic dose) in combination with talazoparib or olaparib had a significantly lower probability of resistance. Furthermore, AsiDNA partially blocks resistance to talazoparib in resistant populations. The results indicate that AsiDNA may be able to abrogate and reverse the acquired resistance to PARPi by normalizing the expression and activity of the proteins involved.