On April 18, 2018 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company discovering and developing Pentarins as a new class of potent and selective cancer medicines, reported that presented data on the efficacy of PEN-866, a novel miniature drug conjugate comprised of a Heat Shock Protein 90 (HSP90) targeting ligand attached through a cleavable linker to SN-38 when combined with Poly ADP ribose polymerase (PARP) inhibitors in preclinical models of human cancer (Press release, Tarveda Therapeutics, 18 18, 2018, View Source [SID1234525520]). SN-38 is a potent topoisomerase 1 inhibitor, and is the active metabolite of irinotecan. The poster titled, "Combination of the miniature drug conjugate PEN-866 with PARP inhibitors as a rational approach to overcoming limitations of PARP inhibitor monotherapy" was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 14-18, 2018 in Chicago.

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The data presented evaluates the use of PEN-866 in combination with PARP inhibitors as an approach to overcoming limitations of PARP inhibitor monotherapy, such as dose limiting toxicities, in preclinical models of human cancer. In efficacy studies carried out in both BRCA mutant and BRCA wildtype tumor xenografts, combinations of PEN-866 and PARP inhibitors resulted in greater efficacy than that of the monotherapy in both tumor types.

"Results presented today show that when combined with PARP inhibitors, PEN-866 could avert the dose limiting toxicities often seen when PARP inhibitors are combined with other anti-cancer therapies," said Richard Wooster, Ph.D., President of Research and Development and Chief Scientific Officer of Tarveda Therapeutics. "The high levels of accumulation and retention of the combination of PEN-866 and a PARP inhibitor in xenograft tumors demonstrate the potential for greater efficacy compared to single agent therapy."

PEN-866’s linker cleavage provides sustained release of SN-38 at a high local tumor concentration leading to DNA damage and apoptosis of tumor cells, which results in broad antitumor activity in a range of preclinical xenograft models. When PEN-866 is administered in combination with PARP inhibitors, the inhibitors reduce DNA repair activity in tumor cells, enabling PEN-866 to maximize its efficacy in damaging cancer cell DNA. A pharmacodynamic assessment of DNA damage performed in tumors responsive to the combination treatment further demonstrated the efficacy of the therapy.

"The mechanistic synergy of PEN-866, carrying the payload SN-38 which is a potent topoisomerase I inhibitor, and PARP inhibitors suggests that this combination therapy could be an attractive approach in the clinical evaluation of PEN-866," said Drew Fromkin, President and Chief Executive Officer of Tarveda Therapeutics. "We look forward to continued studies of PEN-866, including our first-in-human Phase 1 clinical trial of PEN-866 to evaluate safety and efficacy."

About PEN-866
PEN-866 exploits the activation of Heat Shock Protein 90 (HSP90) in tumors to accumulate and release its potent anti-cancer payload, SN-38. PEN-866 is a miniature conjugate that comprises a small molecule, HSP90-targeting ligand linked to SN-38, the active metabolite of irinotecan. The conjugate accumulates and is retained in tumors and, by way of a sustained release of SN-38, causes prolonged DNA damage and tumor regressions in multiple patient-derived and other xenograft tumor models. PEN-866 is currently being studied in first-in-human clinical trials to evaluate safety and efficacy in patients with advanced solid tumors.

About Pentarins
Tarveda is developing Pentarins, potent and selective miniature drug conjugates with high affinity for specific cell surface and intracellular targets. Pentarins are engineered to bind to their tumor cell targets and provide sustained release of their potent therapeutic payloads deep into solid tumor tissue. Comprised of a targeting ligand conjugated to a potent cancer cell killing agent through a tuned chemical linker, Pentarins are designed to overcome the deficits of both larger antibody drug conjugates and small molecules that limit their therapeutic effectiveness against solid tumors. Together, the components of Tarveda’s Pentarins have distinct, yet synergistic, anticancer attributes: the small size of Pentarins allows for rapid and deep penetration into the tumor tissue, the ligand’s targeting ability allows for specific binding and retention in tumor cells, and the chemical linker is tuned to optimize the release of the potent, cell killing payload inside the cancer cells for efficacy.

On April 18, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that its Management Board, with the approval of the Supervisory Board, has resolved to increase the share capital of MorphoSys AG by issuing 2,075,000 new ordinary shares from the authorized capital 2017-II, excluding pre-emptive rights of existing shareholders, to implement the initial public offering in the United States of 8,300,000 American Depositary Shares ("ADSs") pursuant to a Registration Statement on Form F-1, as amended, filed with the U.S. Securities and Exchange Commission (Press release, MorphoSys, APR 18, 2018, View Source [SID1234556336]). Furthermore, MorphoSys has granted the underwriters a 30-day option to purchase additional ADSs of up to 15% of the total number of ADSs placed in the offering (i.e. 1,245,000 additional ADSs). Each ADS will represent 1/4 of a MorphoSys ordinary share. The new ordinary shares underlying the ADSs represent 8.1% (including the underwriters’ option to purchase additional ADSs) of the registered share capital of MorphoSys prior to the consummation of the capital increase.

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Pricing of the offering is expected to occur on April 18, 2018, following the end of the bookbuilding in the United States.
Within the United States of America, the securities referred to in this release are offered only by means of a prospectus. A copy of the prospectus can be obtained from Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 1-212-902-9316 or by e-mailing [email protected]; J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, telephone: 1-866-803-9204; Leerink Partners LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525, ext. 6132, or by e-mailing [email protected].

A registration statement relating to these securities has been filed with the Securities and Exchange Commission but has not yet become effective. These securities may not be sold nor may offers to buy be accepted prior to the time the registration statement becomes effective.

The 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) is being held in Chicago. Here’s a roundup of some of company news (Press release, BioSpace, APR 18, 2018, View Source [SID1234525504]).

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Tokyo, Japan and London-based Sosei Group released new preclinical data for AZD4635, a selective, orally available, small molecule adenosine A2A receptor antagonist. It was discovered by the company’s subsidiary Heptares Therapeutics. AstraZeneca licensed the global rights to the compound in 2016. The drug is now in a Phase I trial as a monotherapy and in combination with AstraZeneca’s Imfinzi (durvalumab) in solid tumors.

Verseon Corporation, headquartered in Fremont, California, presented preclinical data for its tubulin inhibitors in cancer, including cancer cells that showed multidrug resistance. The company utilizes a computer-driven drug discovery platform with a comprehensive chemistry and biology workflow to design new drug candidates. "We are very encouraged by these preclinical results," said Mohan Siviraja, associate director of Biology for Verseon, in a statement. "Multidrug resistance is one of the main reasons why chemotherapies fail. The insensitivity of our compounds to the major transporters and to the overexpression of beta-III tubulin may help us address the need for a more effective, precise therapy."

Rgenix, based in New York, released preclinical data of its RGX-202 in colorectal cancer and other cancers. The compound inhibits SLC6a8, a creatine transporter important to tumor metabolism. The drug was studied alone and in combination with standard chemotherapy agents, such as 5-FU. "The data presented today is just a snapshot of our preclinical progress on our research of RGX-202," said Masoud Tavozoie, Rgenix’ chief executive officer, in a statement. "These data show the strong potential for RGX-202 and support further research of the compound. With these data, we are building a strong foundation for future clinical development of RGX-202, which, with regulatory approval, would diversify our clinical pipeline."

Roswell Park Comprehensive Cancer Center scientists in Chicago have identified epigenetic markers in the breast cancer tumors of African-American women and women of European descent. Christine Ambrosone, professor of Oncology and senior vice president of Population Sciences and chair of Cancer Prevention & Control at Roswell, were interested in epigenetic changes, the ways in which genes are turned on or off in response to environment and other factors. Lead author of the study, Matthew Buas, assistant professor of Oncology in the Roswell Department of Cancer Prevention and Control, said in a statement, "Our findings suggest that epigenetic differences between African-American women and women of European ancestry are important in breast cancer pathogenesis, and may underlie observed differences in the incidence of breast cancer subtypes by race."

Xencor, headquartered in Monrovia, California, presented preclinical data on XmAb24306, an IL15/IL15 receptor alpha complex fused to a bispecific XmAb Fc domain for the treatment of several different cancers. The data showed the complex improved the duration and magnitude of T and NK cell proliferation in vitro and in vivo.

"The plug and play nature of our XmAb technology provides tremendous opportunity to build a suite of tumor microenvironment activators with tunable potency and sustained activity, which have the potential for improved performance over current approaches," said Bassil Dahiyat, president and chief executive officer of Xencor, in a statement. The company expects to file an IND in 2019.

CytRx, based in Los Angeles, presented three posters about its albumin binding ultra high potency Linker Activated Drug Release (LADR) drug candidates, LADR-7, LADR-8, LADR-9 and LADR-10. The technology allows drugs to molecularly bind to albumin in the bloodstream and controls its release at the tumor site. Felix Kratz, the company’s vice president of Drug Discovery, stated, "This technology allows for the delivery of higher doses of drug directly to the tumor, while avoiding much of the off-target toxicity observed with the parent molecules."

MabVax Therapeutics, located in San Diego, presented three posters about its antibody development programs. Paul Maffuid, MabVax’ executive vice president of Research and Development, stated, "We successfully shared the significant progress we have made through these clinical and preclinical studies that continue to establish our growing body of data supporting the development of MVT-1075 for the treatment of pancreatic cancer and other CA19-9 cancers, MVT-2163 as a immunoPET imaging agent, and our most advanced research program focused on the Tn and sTn cancer antigen targets."

InteRNA Technologies, based in Utrecht, Netherlands, presented proof-of-concept data on INT-1B3. INT-1B3 is a lipid nanoparticle formulation of microRNA 193a-3p mimic that can be delivered to cancer cells. MicroRNA 193a-3p is a known tumor suppressor for several cancers. "Overall these data strongly support the unique potential of microRNAs, and INT-1B3 in specific, as a novel therapeutic modality in cancer that acts as a ‘combination treatment in one drug,’" said Roel Schaapveld, InteRNA’s chief executive officer, in a statement. "It is an important milestone for InteRNA because it validates our microRNA platform and demonstrates the focus and commitment of the team over the last years."

On April 18, 2018 AstraZeneca reported that the US Food and Drug AdministrationNSCLC (FDA) has approved Tagrisso (osimertinib) for the 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) mutations, (exon 19 deletions or exon 21 L858R mutations), as detected by an FDA-approved test (Press release, AstraZeneca, APR 18, 2018, View Source [SID1234525521]).The approval is based on results from the Phase III FLAURA trial, which were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress and published in the New England Journal of Medicine.

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Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit at AstraZeneca, said: "Today’s FDA approval of Tagrisso in the 1st-line setting is an exciting milestone for patients and our company. Tagrisso delivered unprecedented median progression-free survival data across all pre-specified patient subgroups, including patients with or without CNS metastases, and could prolong the lives of more patients without their tumours growing or spreading."

Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA trial, from Winship Cancer Institute of Emory University, Atlanta, said: "The approval of osimertinib in the 1st-line setting represents a major advance in the treatment of patients with EGFR mutations and a significant change in the treatment paradigm. Osimertinib provides robust improvements in progression-free survival with no unexpected safety signals compared to the previous generation of EGFR inhibitors."

The FLAURA trial compared Tagrisso to current 1st-line EGFR tyrosine kinase inhibitors (TKIs), erlotinib or gefitinib, in previously-untreated patients with locally-advanced or metastatic EGFR-mutated (EGFRm) NSCLC. Tagrisso met the primary endpoint of progression-free survival (PFS) (see table below). PFS results with Tagrisso were consistent across all pre-specified patient subgroups, including in patients with or without central nervous system (CNS) metastases. Overall survival data were not mature at the time of the final PFS analysis.

Safety data for Tagrisso in the FLAURA trial were in line with those observed in prior clinical trials. Tagrisso was generally well tolerated, with Grade 3 or higher adverse events (AEs) occurring in 34% of patients taking TAGRISSO and 45% in the comparator arm. The most common adverse reactions (≥20%) in patients treated with Tagrisso were diarrhoea (58%), rash (58%), dry skin (36%), nail toxicity (35%), stomatitis (29%), fatigue (21%) and decreased appetite (20%).

In the US, Tagrisso is already approved for the 2nd-line treatment of patients with metastatic EGFRm NSCLC, whose disease has progressed on or after a 1st-line EGFR-TKI therapy and who have developed the secondary T790M mutation, as detected by an FDA-approved test. In 2017, Tagrisso was granted Breakthrough Therapy and Priority Review designations by the US FDA in the 1st-line treatment setting. Tagrisso is under regulatory review in the European Union and Japan for use in the 1st-line treatment setting with regulatory decisions anticipated in the second half of 2018.

Tagrisso received its first approval for 1st-line use based on the FLAURA data in Brazil in patients with metastatic EGFRm NSCLC on April 16, 2018

NOTES TO EDITORS
About NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with EGFR-TKIs, which block the cell-signalling pathways that drive the growth of tumour cells. Tumours almost always develop resistance to EGFR-TKI treatment, however, leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib, erlotinib and afatinib due to the EGFR T790M resistance mutation. There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFRm NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About Tagrisso

Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases. Tagrisso 40mg and 80mg once-daily oral tablets have been approved in the US and Brazil for 1st-line EGFRm advanced NSCLC, and in more than 75 countries including the US, EU, Japan and China for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant setting and in combination with other treatments.

About the FLAURA trial

The FLAURA trial assessed the efficacy and safety of Tagrisso 80mg once daily vs. standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC. The trial was double-blinded and randomised, with 556 patients across 29 countries.

About AstraZeneca in Lung Cancer

AstraZeneca is committed to developing medicines to help every patient with lung cancer. We have three approved medicines and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth platform for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On April 18, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to CB-839 in combination with cabozantinib for the treatment of patients with metastatic renal cell carcinoma who have received one or two prior lines of therapy, including at least one vascular endothelial growth factor tyrosine kinase inhibitor or the combination of nivolumab and ipilimumab (Press release, Calithera Biosciences, APR 18, 2018, View Source [SID1234535241]). CB-839 is a first-in-class, oral, selective, potent inhibitor of glutaminase being evaluated in the CANTATA trial. The trial is a randomized double-blind clinical study of cabozantinib in combination with CB-839 or placebo in 298 patients with clear cell renal cell carcinoma. The primary endpoint is progression free survival and the global study is open for enrollment.

"Despite a number of new therapies for the treatment of renal cell carcinoma, there remains a significant unmet need among advanced patients who have received prior treatment," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "We are pleased that CB-839 has been granted Fast Track designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our glutaminase inhibitor as an important new therapy for patients with advanced or metastatic renal cell carcinoma who have failed prior systemic therapy."

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The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of drugs and biologics, to treat serious or life threatening conditions, and to fill an unmet medical need. Specifically, Fast Track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support approval, and also provides the opportunity to submit sections of an NDA on a rolling basis as data become available. About CB-839 Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents.