On March 25, 2019 Veracyte, Inc. (Nasdaq: VCYT) reported that new data from the Afirma Xpression Atlas suggest that the majority of newly diagnosed medullary thyroid cancers (MTC) are associated with variants from three genes (Press release, Veracyte, MAR 25, 2019, View Source [SID1234534592]). The findings shed new light on the genomic underpinning of this rare, but aggressive, form of thyroid cancer and were presented today at ENDO 2019, the Endocrine Society’s annual meeting, which is being held March 23-26 in New Orleans.

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"Our findings are important because they help us better understand the genomic drivers of medullary thyroid cancer," said Steven G. Waguespack, M.D., professor of internal medicine and pediatrics at University of Texas MD Anderson Cancer Center in Houston, who presented the new data in a guided poster session. "Moreover, this information, derived from a fine needle aspiration biopsy specimen, may help guide physicians in the preoperative evaluation, surgical planning and targeted therapy selection for patients diagnosed with this disease."

For the study, researchers evaluated 77 preoperative fine needle aspiration biopsies from thyroid nodules that were positive for MTC based on Afirma testing and which spanned a range of Bethesda System cytology classification categories (III-VI). All cases were subsequently evaluated with the Xpression Atlas, which uses RNA whole-transcriptome sequencing to detect 761 variants and 130 fusions in 511 genes that are associated with thyroid cancer. The scientists found that among the MTC cases, 55.8 percent harbored a RET variant, 9.1 percent included a KRAS variant, 7.8 percent contained an HRAS variant (some of which contained more than one of these gene alterations), while 2.6 percent of cases possessed fusions and 26.0 percent included no gene variants or fusions.

"As more is understood about the genomic makeup of thyroid cancer biology, physicians may be able to further refine their treatment plans for patients using ever-more-granular genomic information," said Giulia C. Kennedy, Ph.D., chief medical and scientific officer at Veracyte. "We believe that our Afirma offering – based on our whole-transcriptome sequencing platform – is well-positioned to serve the needs of physicians in the expanding era of precision medicine."

On March 25, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage immuno-oncology company, reported that IMV Chief Executive Officer Frederic Ors will present at the Spring Investor Summit and the HC Wainwright Global Life Sciences Conference during April 2019 (Press release, IMV, MAR 25, 2019, IMV Inc. to Present at Two Upcoming Investor Conferences [SID1234534608]).

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Details on each conference and presentation are as follows:

Venue: Spring Investor Summit, being held April 1-2, 2019

Date of Presentation: Monday, April 1

Time: 8:30 a.m. ET

Location: JW Marriott Hotel, Essex House, New York City

Venue: HC Wainwright Global Life Sciences Conference, being held April 7-9, 2019

Date: Tuesday, April 9, 2019

Time: 10:40 a.m. BST

Location: Stratton Suite, Grosvenor House, A JW Marriott Hotel, London, UK

There will be a live webcast of both of these presentations available in the events, presentations and webcasts section of IMV’s website. Following the presentations, the webcasts will be archived for 90 days and a copy of the presentations will remain available in the same section of the website.

On March 25, 2019 Onconova Therapeutics, Inc. (Nasdaq: ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing small molecule drug candidates to treat cancer reported that it has surpassed the 75 percent enrollment milestone in its pivotal Phase 3 trial of rigosertib for the potential treatment of high-risk myelodysplastic syndromes (HR-MDS), a study known as INSPIRE (Press release, Onconova, MAR 25, 2019, View Source [SID1234534593]).

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"We are pleased to have passed the 75 percent completion of enrollment milestone and are on track with our anticipated timeline for completion of accrual to the INSPIRE study in the second half of 2019," said Dr. Richard Woodman, Onconova’s Chief Medical Officer and Senior Vice President of Research & Development. "Rigosertib has the potential to be the first new MDS treatment in more than 15 years for a condition afflicting an estimated 59,000 patients in the United States."

Dr. Steven M. Fruchtman, President and CEO of Onconova, stated, "Clinical execution including completing our INSPIRE study remains our top priority. In addition to near-term milestones for the INSPIRE study, we are advancing business development discussions and remain on track to reach other important clinical milestones throughout 2019 and into 2020. This includes advancing our oral rigosertib program in MDS. We are grateful to patients and to our valued partners for their participation in the important INSPIRE study, and look forward to completing patient enrollment later this year."

The INSPIRE study is a Phase 3, open label, randomized, controlled, international study designed to determine the efficacy, safety and tolerability of single agent intravenous (IV) rigosertib to treat second-line higher-risk MDS patients. The trial includes patients under the age of 82 who have progressed on, relapsed, or failed to respond to previous treatment with hypomethylating agent (HMA) therapy within nine cycles over the course of one year after initiation of HMA therapy. Patients are randomized to receive either rigosertib with best supportive care, or the physician’s choice of therapy with best supportive care. The primary endpoint of the study is the sequential analysis of overall survival of all randomized patients in the intent-to-treat population, and the International Prognostic Scoring System – Revised (IPSS-R) Very High-Risk subgroup. Based on the promising survival signal observed by the Independent Data Monitoring Committee at interim analysis in early 2018, the Committee recommended that the trial continue with an expansion in enrollment to 360 patients based on a pre-planned sample size re-estimation.

Persons interested in participating in the INSPIRE study can obtain more information by visiting View Source

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are conditions that can occur when the blood-forming cells in the bone marrow become dysfunctional and thus produce an inadequate number of circulating blood cells. It is frequently associated with the presence of blasts or leukemic cells in the marrow. This leads to low numbers of one or more types of circulating blood cells, leading to the need for blood transfusions. In MDS, some of the cells in the bone marrow are abnormal (dysplastic) and may have genetic abnormalities associated with them. Different cell types can be affected, although the most common finding in MDS is a shortage of red blood cells (anemia). Patients with higher-risk MDS may progress to the development of acute leukemia.

On March 25, 2019 F-star, a clinical-stage biopharmaceutical company pioneering the development of novel tetravalent bispecific antibodies that target the immune system to fight cancer, reported that new preclinical data on three immuno-oncology programmes will be presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta, US, held from 29 March – 03 April 2019 (Press release, f-star, MAR 25, 2019, View Source [SID1234534609]).

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Neil Brewis, CSO of F-star said "We are excited about this new preclinical data, as it demonstrates the full potential of our tetravalent molecules to leverage a superior anti-tumour response compared to other checkpoint monotherapies, alone or in combination. In addition, our drugs harness a potentially safer mode of action, independent of FcγR-binding, which has been reported to drive systemic cytotoxicity."

FS120 and FS222 are two proprietary F-star assets targeting members of the Tumour Necrosis Factor Receptor Super Family (TNFRSF). FS120 is a first-in-class dual agonist mAb² simultaneously targeting OX40 (CD134, TNFRSF4) and CD137 (4-1BB) while FS222 is an agonist/antagonist mAb² against CD137/PD-L1 (Programmed Death-Ligand 1). Both are on track for IND filings this year.

The preclinical presentations illustrate the synergistic benefit of F-star’s tetravalent mAb² and how both FS120 and FS222 individually outperform combinations of single agents in multiple assays. Furthermore, and in contrast to broader CD3-mediated immune stimulation, F-star programmes promote a more controlled activation of immune effectors. The mAb² also benefit from a safer FcγR-independent profile, especially regarding dose-limiting hepatotoxicity, as supported by data to be presented on FS222.

Finally, F-star will also share preclinical data on a third programme, FS118, a potentially first-in-class bispecific antagonist of LAG-3 (Lymphocyte-Activation Gene 3) and PD-L1. The poster describes FS118’s potential to increase response rates by overcoming the LAG-3-mediated tumour evasion mechanism that often takes place following single agent checkpoint blockade. FS118 is currently investigated in a Phase 1 study in patients who have progressed on or after prior PD-1/PD-L1 containing therapy.

Eliot Forster, CEO of F-star said "We are creating a paradigm shift in the future of cancer treatment and believe our drugs will offer meaningful benefits to patients who are currently poorly responding or non-eligible to other immuno-oncology therapies. In addition, the mAb² format is poised to become a game changer in the industrial landscape, as it maintains the well-established and favourable manufacturing properties of IgG antibodies."

FS118 is under an exclusive option to Merck KGaA, Darmstadt, Germany.

Details of the posters are below:

FS120 communication: Dual agonist bispecific antibody targeting OX40 and CD137 mediates anti-tumour immunity and synergises with PD-1/PD-L1 blockade to improve survival in a syngeneic mouse model

Session Category: Immunology
Session Title: Therapeutic Antibodies 3
Session Date and Time: 01 Apr from 13:00 – 17:00
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 25
Poster Board Number: 22
Abstract Number: 2398

FS222 communication: FS222 mAb2, a bispecific conditional agonist antibody targeting CD137 and PD-L1, induces potent lymphocyte activation and has a favourable safety profile

Session Category: Immunology
Session Title: Therapeutic Antibodies 2
Session Date and Time: 01 Apr from 08:00 – 12:00
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 25
Poster Board Number: 09
Abstract Number: 1540

FS118 communication: LAG-3/PD-L1 mAb2 can overcome PD-L1-mediated compensatory upregulation of LAG-3 induced by single-agent checkpoint blockade

Session Category: Immunology
Session Title: Therapeutic Antibodies 3
Session Date and Time: 01 Apr from 13:00 – 17:00
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 25
Poster Board Number: 23
Abstract Number: 2399

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.