On May 15, 2018 vTv Therapeutics Inc. (Nasdaq:VTVT) reported financial and operational results for the first quarter that ended March 31, 2018 (Press release, vTv Therapeutics, MAY 15, 2018, View Source;p=RssLanding&cat=news&id=2349259 [SID1234526656]).

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"We continue to make progress on all of our major programs," said Steve Holcombe, chief executive officer, vTv Therapeutics. "While our initial readout of the results of our STEADFAST Part A Study was not what we had hoped for, we are pleased with the results of our subgroup analysis and are continuing our work in preparation for the Part B readout with a new prospectively-defined target population. We also are continuing to move our diabetes compounds into Phase 2 studies. Our GKA activator is now enrolling patients in a Phase 2 trial for type 1 diabetes and we expect interim results by year-end. We also continue to work with Huadong Medicine in China on the commencement of a Phase 2b study for our GLP-1r compound to test lower dosing levels. We remain enthusiastic for the success of these programs."

Pre-specifying New Subgroup with the FDA for Part B Readout Expected in June

Last week, the company announced that, based on post hoc analyses of the data from Part A of the company’s Phase 3 STEADFAST study of the investigational medication azeliragon in people with mild Alzheimer’s disease, despite not meeting co-primary endpoints, it had identified a subpopulation that showed statistically significant benefit (unadjusted for multiple post hoc comparisons) from azeliragon relative to placebo on ADAS-cog. The identified subpopulation consisted of participants with peak azeliragon blood plasma concentration of less than 7.5 ng/mL.

Based on the subpopulation data analyses from the Part A Study and the prior azeliragon trials, the company will submit a revised Statistical Analysis Plan (SAP) to the Food and Drug Administration for the Part B Study that pre-specifies a target population for the primary study analysis and expects to report Part B topline efficacy results based on 12 month data in June 2018.

The patients in the identified subgroup (n=~48) had a -1.9 point improvement in ADAS-cog relative to the placebo group (n=200) which was statistically significant (unadjusted for multiple post hoc comparisons) (p = 0.02), and a 0.5 point improvement on CDR-sb relative to placebo (p = .06) despite the smaller sample size.

First Quarter 2018 Financial Results

Cash Position: Cash and cash equivalents as of March 31, 2018, were $6.5 million compared to $11.8 million as of December 31, 2017.
R&D Expenses: Research and development expenses were $8.9 million in the first quarter of 2018, compared to $10.1 million in the fourth quarter of 2017. The decrease in research and development expenses were primarily driven by decreased costs related to certain azeliragon preclinical studies which were completed in the fourth quarter of 2017. Additionally, research and development expenses related to compound manufacturing costs for azeliragon as well as the STEADFAST and OLE studies were lower during the first quarter of 2018.
G&A Expenses: General and administrative expenses were $2.3 million and $2.9 million, for the first quarter of 2018 and the fourth quarter of 2017, respectively. The decrease in general and administrative cost was primarily due to lower incentive compensation costs in the first quarter of 2018 as well as lower expenses related to professional services. The cost of professional services were higher in the fourth quarter of 2017 due to the license transactions that were entered into in December 2017.
Net Loss Before Non-Controlling Interest: Net loss before non-controlling interest was $10.0 million for the first quarter of 2018 compared to net loss before non-controlling interest of $14.6 million for the fourth quarter of 2017.
Net Loss per Share: GAAP net loss per share was $0.30 and $0.44 for the three months ended March 31, 2018 and December 31, 2017, respectively, based on weighted-average shares of 9.7 million in each period. Non-GAAP net loss per fully exchanged share was $0.30 and $0.44 for the three months ended March 31, 2018 and December 31, 2017, respectively, based on non-GAAP fully exchanged weighted-average shares of 32.8 million in each period.

On May 15, 2018 Celsius Therapeutics, a company translating single-cell genomic insights into precision therapeutics for autoimmune diseases and cancer, reported with a $65 million Series A financing led by Third Rock Ventures with participation from GV (formerly Google Ventures), Heritage Provider Network, Casdin Capital, Alexandria Venture Investments and other key investors (Press release, Celsius Therapeutics, MAY 15, 2018, View Source [SID1234526810]). Celsius is charting a new course of target and drug discovery by understanding the specific cells, among many others, that are key players in disease and by identifying the genes that are triggering their malfunction.

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Celsius’ fundamentally new approach aims to combine the power of single-cell genomic sequencing with computational algorithms to discover first-in-class precision therapies that have a transformative impact on the lives of patients with autoimmune diseases and cancer. To do this, the company applies a systematic approach, starting with single-cell sequencing on defined patient samples to identify and understand the individual cells and their interactions that cause dis-ease.

By analyzing single cells, Celsius’ approach has the potential to understand the causes of disease at an entirely new level of resolution that overcomes limitations of traditional genomic sequencing approaches. Celsius believes this approach could be the key to bring precision medicines to autoimmune diseases for the first time. These cellular insights could also allow Celsius to identify the right combination of treatments for the right patients and build on the promising results seen in the field of immunooncology.

Celsius was co-founded by Aviv Regev, Ph.D., core institute member, chair of the faculty and director of the Klarman Cell Observatory at the Broad Institute of MIT and Harvard, Professor of Biology at MIT and an investigator at the Howard Hughes Medical Institute. Her research revealed that many diseases are driven by the combined dysfunction of several specific cell types, and the interactions between them. Traditional genomic sequencing cannot identify these individual contributions, as only the average can be seen and key critical causes can be missed. For the first time, with the approaches discovered by Aviv and Celsius’ other founders, the company will combine massive datasets of unprecedented size and complexity with sophisticated machine learning algorithms. Celsius will be able to distinguish the specific cells, among many others, that play a key role in disease and identify the genes that are triggering their malfunction. This approach will allow the company to more efficiently identify specific targets for treating diseases in specific patients and ultimately develop medicines for those targets.

"When first meeting with Aviv and her colleagues and learning about the significance of this new technology, we knew this had to become a company. We formed Celsius with the goal of bringing a novel precision medicine approach to underserved patients with autoimmune diseases and certain cancers," said Christoph Lengauer, Ph.D., co-founder and president of Celsius and venture partner at Third Rock Ventures. "With the new level of clarity provided by single-cell sequencing, our team will be able to address many of the challenges of the current treatments and introduce a new class of medicines that will lead to better outcomes and potential cures."

Expert Team of Scientists and Clinicians

Celsius’ founders are established leaders with experience across the company’s entire product engine, from single-cell RNA sequencing to computational biology, disease biology and drug discovery.

• Jeffrey Bluestone, Ph.D., president and chief executive officer, Parker Institute for Cancer Immunotherapy, University of California, San Francisco; A.W. and Mary Margaret Clausen Distinguished Professor

• Vijay Kuchroo, D.V.M., Ph.D., Samuel L. Wasserstrom professor of neurology, Harvard Medical School; senior scientist, neurology, Brigham and Women’s Hospital; associate member, Broad Institute; director, Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital

• Christoph Lengauer, Ph.D., venture partner, Third Rock Ventures; president, Celsius Therapeutics; adjunct associate professor, Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University School of Medicine

• Aviv Regev, Ph.D., Chair of the Faculty and core institute member, and director, Klarman Cell Observatory, Broad Institute; professor, Department of Biology, MIT; Investigator, Howard Hughes Medical Institute

• Ramnik Xavier, M.D., chief of gastroenterology, Massachusetts General Hospital; institute member, Broad Institute; Kurt Isselbacher professor of medicine, Harvard Medical School

Celsius has licensed key technologies from the Broad Institute based on the work of Drs Regev and Kuchroo, including non-exclusive licenses to single-cell technologies and an exclusive license to early stage therapeutic programs.

"Each of us is made up of tens of trillions of cells. At the core of founding Celsius was the new ability to see something we could not see before. We can now see the dysfunction of key cells and their interactions within their neighborhood. Diseases that we have struggled to understand now can become crystal clear. With that clarity, we hope to create novel precision medicines," said Alexis Borisy, partner at Third Rock Ventures and chairman of Celsius Therapeutics. "We believe this approach and the incredible group that has been assembled by the founders have the unique potential to deliver a powerful new class of medicines and make a meaningful difference for patients."

On May 14, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported that members of the management team will present at the following upcoming investor conferences (Press release, Deciphera Pharmaceuticals, MAY 14, 2018, View Source [SID1234526560]):

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UBS Global Healthcare Conference on Monday, May 21, 2018 at 8:30 AM ET. The conference is being held at the Grand Hyatt New York in New York City.
Jefferies Global Healthcare Conference on Thursday, June 7, 2018 at 1:30 PM ET. The conference is being held at the Grand Hyatt New York in New York City.
A live webcast of the events will be available on the "Events and Presentations" page in the "Investors" section of the Company’s website at View Source A replay of the webcasts will be archived on the Company’s website for 90 days following the presentation.

On May 14, 2018 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology, reported new scientific advisors in immuno-oncology and autoimmunity (Press release, Intellia Therapeutics, MAY 14, 2018, View Source [SID1234526584]). The advisors hail from prestigious international institutions and collectively have both scientific and clinical expertise in cell therapies in these areas.

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"The advisors we’ve assembled include researchers and physicians who are luminaries in their fields," said Intellia President and Chief Executive Officer John Leonard, M.D. "Pursuing both in vivo and ex vivo pipelines, Intellia has a broad spectrum approach to genome editing in a variety of therapeutic applications using our CRISPR/Cas9 technology. We look forward to working alongside these experts and benefiting from their deep experience and insight, to drive development of our wholly owned ex vivo programs in immuno-oncology and autoimmunity."

The following scientific leaders and clinicians are Intellia’s advisors on ex vivo cell therapy in immuno-oncology:

Evren Alici, M.D., Ph.D., assistant professor and group leader, hematology, Karolinska Institutet, Sweden

Chiara Bonini, M.D., Ph.D., full professor, Università Vita-Salute San Raffaele; deputy director, Division of Immunology, Transplantation and Infectious Diseases, Ospedale San Raffaele; and head, Experimental Hematology Unit, Ospedale San Raffaele, Italy

Daniel DeAngelo, M.D., Ph.D., associate professor of medicine, Harvard Medical School, and director, clinical and translational research, adult leukemia, Dana Farber Cancer Institute, United States

Saar Gill, M.D., Ph.D., assistant professor of medicine, Center for Cellular Immunotherapies, University of Pennsylvania, United States

Johanna Olweus, M.D., Ph.D., full professor and head, Department of Cancer Immunology, University of Oslo, and director, K.G. Jebsen Center for Cancer Immunotherapy, Norway

E. John Wherry, Ph.D., Richard and Barbara Schiffrin President’s Distinguished Professor of Microbiology, and director, Institute for Immunology, University of Pennsylvania, United States

Juan Carlos Zúñiga-Pflücker, Ph.D., professor and chair, Department of Immunology, University of Toronto, and senior scientist, Sunnybrook Research Institute, Canada
These experts are Intellia’s advisors on ex vivo cell therapy in autoimmunity:

Laurence Turka, M.D., chief scientific officer, Rheos Medicines; deputy director, Immune Tolerance Network; and professor of surgery and medicine (part-time), Massachusetts General Hospital and Harvard Medical School, United States

Kathryn Wood, D.Phil., F.Med.Sci., emeritus professor of immunology, Nuffield Department of Surgical Sciences, University of Oxford, United Kingdom

On May 14, 2018 CStone Pharmaceuticals (CStone) reported dosing of the first patient in a Phase I clinical trial in Australia for CS1003, an investigational anti-programmed death-1 (PD-1) monoclonal antibody (mAb) (Press release, CStone Pharmaceauticals, MAY 14, 2018, View Source [SID1234526640]). The open-label, first-in-human (FIH) study is initiated at Scientia Clinical Research Ltd in Australia and will investigate the safety, tolerability, and preliminary efficacy of CS1003 in patients with advanced solid tumors.

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"We are excited to announce initiation of clinical development for PD-1 inhibitor CS1003, our second pipeline candidate to enter Phase I studies in Australia after the CTLA-4 mAb CS1002 within one month," said Dr. Frank Jiang, Chief Executive Officer at CStone. "CS1003 is cross-reactive with human and mouse PD-1 which enables quick pre-clinical proof of concept experiments in combination with novel targets, leading to global first-in-combination potential. Because of this unique feature, CS1003 is critical to CStone’s combination strategy in cancer immunotherapy."

The launch of clinical studies for CS1003 is a key milestone for CStone, which now has three important checkpoint inhibitors for cancer therapy under clinical development. Alongside CS1001 (PD-L1) and CS1002 (CTLA-4), CS1003 will provide the backbone for CStone’s pipeline development of oncology combination therapies.

As noted by Dr. Jason Yang, Chief Medical Officer of CStone, "In preclinical studies, CS1003 demonstrated high affinity and selectivity for PD-1, as well as synergistic anti-tumor effects with multiple small-molecule drugs in animal models. The launch of this clinical program will allow us to gather important safety and efficacy data on CS1003. This will lay the foundation for future development of this molecule, in particular as the basis of combination therapies."

"We are excited to be enrolling our first patient treated with CS1003 and are hopeful that this novel immunotherapy drug will add to the available therapeutic options for advanced-stage tumors, either by itself or in combination with other drugs," said Dr. Charlotte Lemech, MBBS, BSc, FRACP, MD, lead investigator for this trial at Scientia Clinical Research Ltd.

The Phase Ia/Ib study includes a dose-escalation stage followed by a dose-expansion stage. Additional information on the trial can be found here.

About CS1003 and the PD-1/PD-L1 pathway

CS1003 is a humanized anti-PD-1 IgG4 monoclonal antibody developed by CStone using an internationally leading hybridoma platform. CS1003 has shown good tolerability and efficacy profile in preclinical in vivo studies.

PD-1, or programmed death-1, is an inhibitory checkpoint receptor expressed on T cells. Under normal circumstances, it binds with its ligands, programmed death ligand-1 or ligand 2 (PD-L1/PD-L2), inhibiting T cell and cytokine activation, serving to dampen the immune response in order to prevent damage to healthy tissues. However, studies have shown that PD-L1 can be abundantly expressed on the surface of many solid tumors as well as hematological malignancies. Cancer cells can therefore make use of the PD-1/PD-L1 pathway to successfully avoid immune system recognition and attack. Targeting of the PD-1/PD-L1 checkpoint by anti-tumor drugs can block the "tumor immune evasion mechanism" and restore anti-cancer immune ability in patients.

Currently, there are two anti-PD-1 antibodies approved globally: Opdivo (nivolumab) from Bristol-Myers Squibb and Keytruda (pembrolizumab) from Merck, Sharp & Dohme. Unlike other anti-PD-1 mAbs, CS1003 recognizes both human and murine PD-1, providing a unique competitive advantage during efficacy testing in syngeneic mouse tumor models particularly for development of effective combination therapies.