On April 4, 2017 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported the presentation of preclinical data of ROLONTIS from a poster presentation session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Spectrum Pharmaceuticals, APR 4, 2017, View Source [SID1234518451]).

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!

"We are excited to see positive data continuing to develop in our highest priority program," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "The data shows that in this preclinical study eflapegrastim was found to be more potent in shortening the duration of severe neutropenia. Eflapegrastim was more potent than pegfilgrastim at G-CSF equivalent doses in neutropenic animal models. We are currently enrolling patients in our pivotal trial and continue to expect a BLA filing next year."

Abstract #1347: In vivo efficacy of eflapegrastim in rats with chemotherapy-induced neutropenia

In this study, rats were treated with 50 mg/kg of cyclophosphamide (CPA) intraperitoneally to induce neutropenia. Pegfilgrastim was administered subcutaneously as a single dose of 100 µg/kg on Day 1 and filgrastim was administered subcutaneously at a dose of 20 µg/kg daily for five days on Days 1 to 5. Eflapegrastim was administered subcutaneously as a single dose on Day 1, at doses ranging from 32 µg /kg to 322 µg/kg (or 8.8 µg/kg to 88 µg/kg as G-CSF equivalent). Blood samples were collected for 8 days after drug administration for the measurement of neutrophil counts and the Duration of Severe Neutropenia (DSN).

Results showed the DSN in neutropenic rats treated with eflapegrastim was compared with the DSN in neutropenic rats treated with pegfilgrastim or filgrastim. The DSN was 0.2 days when eflapegrastim was administered as a single dose at 88 µg/kg (as G-CSF equivalent) 24 hours after administering CPA. In contrast, the DSN was 3.04 days with filgrastim administered at a dose of 20 µg/kg for 5 days from Day 1 to Day 5 and 2.8 days with pegfilgrastim administered as a single dose of 100 µg/kg 24 hours after administering CPA. At the lowest eflapegrastim dose of 8.8 µg/kg that was about 1/10 of G-CSF equivalent dose for pegfilgrastim, the DSN in eflapegrastim-treated rats was 2.94 days. Thus, eflapegrastim was found to be more potent in shortening the DSN with a lower G-CSF equivalent dose when compared to either pegfilgrastim or filgrastim.

On April 4, 2017 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform, reported the presentation of data informing the design of a first-in-patient clinical trial for PRS-343, a first-in-class 4-1BB/HER2 bispecific in a poster session at the 2017 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR (Press release, Pieris Pharmaceuticals, APR 4, 2017, View Source [SID1234518450])).

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!

Complementing previously disclosed preclinical data demonstrating that PRS-343 elicits robust T cell expansion in the tumor microenvironment while avoiding unwanted peripheral T cell activation in HER2-positive cancer models, the data presented today demonstrate:

PRS-343 elicited robust T cell activation when engaging HER2 on cell lines derived from tumors resistant to trastuzumab therapy, as well as tumor cell lines with elevated HER2 expression in the IHC 2+ range
4-1BB-mediated T cell activation by PRS-343 resulted in the expression of a broad spectrum of inflammatory cytokines associated with anti-tumor immune responses
PRS-343 was well tolerated and led to no significant findings in IND-enabling preclinical safety and non-human primate toxicology studies
Today’s presented data suggest the clinical potential of PRS-343 in a broad population of patients with HER2-expressing cancers," commented Louis Matis, MD, Chief Development Officer of Pieris. "Moreover, the preclinical pharmacokinetic and safety profile of PRS-343 supports the initiation of clinical development, which we anticipate during the first half of this year." A copy of the poster can be viewed here.

About PRS 343:
PRS-343 is a bispecific monoclonal antibody/Anticalin fusion protein comprised of a HER2 tumor-targeting mAb genetically linked to a potent Anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes (TILs), and is, therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.

On April 4, 2017 RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, reported that the U.S. Food and Drug Administration (FDA) has granted YELIVA (ABC294640) Orphan Drug designation for the treatment of cholangiocarcinoma (Press release, RedHill Biopharma, APR 4, 2017, View Source [SID1234518446]).

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 Orphan Drug designation allows RedHill to benefit from various development incentives to develop YELIVA for this indication, including tax credits for qualified clinical testing, waiver of a prescription drug user fee (PDUFA fee) upon submission of a potential marketing application and, if approved, a seven-year marketing exclusivity period for the treatment of cholangiocarcinoma.

YELIVA is a Phase II-stage, proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities, targeting multiple oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation.

Mark L. Levitt, MD, PhD, RedHill’s Medical Director, Oncology, said: "Cholangiocarcinoma is a cancer with a poor prognosis. Patients suffering from this disease have very few treatment options, and they are of limited efficacy. Based on promising preclinical data, as well as results from three previously treated cholangiocarcinoma patients who took part in the Phase I study with YELIVA, we are hopeful that YELIVA could potentially provide a much-needed new treatment option for patients. We are very pleased with the Orphan Drug designation and are advancing our preparations for a Phase IIa study to evaluate the safety and efficacy of YELIVA in patient suffering from unresectable, intrahepatic and extrahepatic cholangiocarcinoma, which we plan to initiate in the third quarter of this year."

Cholangiocarcinoma (bile duct cancer) is a highly lethal malignancy for which there is a strong need for more effective systemic treatments. Approximately 8,000 people are diagnosed with intrahepatic and extrahepatic bile duct cancers annually in the U.S.1, with recent studies showing an increased incidence of cholangiocarcinoma, mainly attributed to recent advancements in diagnosis of this disease2. Surgery with complete resection remains the only curative therapy for cholangiocarcinoma, however only a minority of patients are classified as having a resectable tumor at the time of diagnosis3. Additional treatment options include radiation therapy and chemotherapy; however, the efficacy of these treatments in cholangiocarcinoma patients is also limited. Despite overall advances in the ability to diagnose and treat patients with cholangiocarcinoma, the prognosis for these relapse patients who have failed initial chemotherapy remains very poor, with an overall median survival of approximately one year4. The 5-year relative survival rates of intrahepatic and extrahepatic cholangiocarcinoma patients range between 2% to 30%, depending on the tumor type and stage at diagnosis5.

Final results from the Phase I study with YELIVA in patients with advanced solid tumors confirmed that the study, conducted at the Medical University of South Carolina (MUSC) Hollings Cancer Center, successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity.

Of the three patients with cholangiocarcinoma treated in the Phase I study, all of whom had prior therapy, one subject achieved a sustained partial response (Overall Survival (OS) = 20.3 months) and the other two subjects had prolonged stable disease (OS = 17.6 and 16.3 months).

RedHill plans to initiate a Phase IIa clinical study with YELIVA in patients with advanced, unresectable, intrahepatic and extrahepatic cholangiocarcinoma in the third quarter of 2017. The single-arm study will evaluate YELIVA as a single agent in cholangiocarcinoma patients with a primary endpoint of determining the response rate of cholangiocarcinoma to this treatment.

A Phase II study with YELIVA for the treatment of advanced hepatocellular carcinoma (HCC) is ongoing at MUSC Hollings Cancer Center. The study is supported by a $1.8 million grant from the NCI, awarded to MUSC, which is intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, with additional support from RedHill.

A Phase Ib/II study with YELIVA for the treatment of refractory or relapsed multiple myeloma is ongoing at Duke University Medical Center. The study is supported by a $2 million grant from the NCI Small Business Innovation Research Program (SBIR) awarded to Apogee Biotechnology Corp. (Apogee), in conjunction with Duke University, with additional support from RedHill.

A Phase I/II clinical study evaluating YELIVA in patients with refractory/relapsed diffuse large B-cell lymphoma as well as Kaposi sarcoma patients is ongoing at the Louisiana State University Health Sciences Center. The study is supported by a grant from the NCI awarded to Apogee, with additional support from RedHill.

A Phase Ib study to evaluate YELIVA as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the third quarter of 2017.

A Phase II study to evaluate the efficacy of YELIVA in patients with moderate to severe ulcerative colitis is planned to be initiated in the second half of 2017.

About YELIVA (ABC294640):

YELIVA (ABC294640) is a Phase II-stage, proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anti-cancer and anti-inflammatory activities. RedHill is pursuing with YELIVA multiple clinical programs in oncology, inflammatory and gastrointestinal indications. By inhibiting SK2, YELIVA blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid signaling molecule that promotes cancer growth and pathological inflammation. SK2 is an innovative molecular target for anticancer therapy because of its critical role in catalyzing the formation of S1P, which is known to regulate cell proliferation and activation of inflammatory pathways. YELIVA was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical studies in oncology, inflammation, GI and radioprotection models, as well as the ABC-101 Phase I clinical study in cancer patients with advanced solid tumors. The Phase I study included the first-ever longitudinal analysis of plasma S1P levels as a potential pharmacodynamic (PD) biomarker for activity of a sphingolipid-targeted drug. The administration of YELIVA resulted in a rapid and pronounced decrease in S1P levels, with several patients having prolonged stabilization of disease. YELIVA received Orphan Drug designation from the U.S. FDA for the treatment of cholangiocarcinoma. The development of YELIVA was funded to date primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including the U.S. National Cancer Institute, the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Defense and the FDA Office of Orphan Products Development.

On April 4, 2017 Kancera AB (publ) has previously announced the Board’s decision to execute the company’s exclusive option to acquire the Fractalkine project from Acturum Real Estate AB after transfer of results and know-how (Press release, Kancera, APR 4, 2017, View Source [SID1234518441]). This transfer of results and know-how has now advanced to the point where a decision has been taken to complete the acquisition of the Fractalkine project from Acturum Real Estate AB.

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!

Payment for the Fractalkine project will be made through an issue in three stages of a total of 6 million shares in Kancera AB. The installments will be made as the project is developed successfully and until the first clinical study has been conducted. The first payment of 2 million shares is due when Kancera AB apply for authorization for a clinical trial.

About the Fractalkine project
Fractalkine is an immune regulatory factor, a so-called chemokine, that sends signals via the CX3CR1 receptor, also called G-protein coupled receptor 13 (GPCR13). The level of fractalkine and its receptor, CX3CR1 has been shown to be elevated in many inflammatory diseases, cancer and in chronic pain conditions. Kancera’s drug candidate KAND567 is the furthest developed drug candidate against CX3CR1 and has been shown to be effective against inflammation and pain in several preclinical disease models. Kancera is now preparing the project for clinical studies.

In the healthy individual, Fractalkine and its receptor, CX3CR1, regulate migration of immune cells from the blood capillary wall into areas where the immune system is needed. Animal studies show that Fractalkine’s receptor is not essential for survival and that important immune functions remain intact despite the lack of receptor.The body of research supports the overall hypothesis that CX3CR1 is more crucial to developing disease than to keeping the individual healthy. The basis for successful development of KAND567 lies in effectively addressing local inflammation while maintaining a healthy immune system.

In clinical trials, blocking of the Fractalkine system has been shown to have the desired effect against auto-immune diseases such as Crohn’s disease and rheumatoid arthritis in refractory patients. These positive studies have been conducted by the pharmaceutical company Eisai using a monoclonal antibody. The results of these studies means that the probability increases for the Kancera AB drug candidate KAND567 to achieve clinical and commercial success as the first small-molecule drug that works through the Fractalkine system to combat many common diseases.