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RedHill Biopharma Provides Semi-Annual Business Update

On April 9, 2018 RedHill Biopharma Ltd. (NASDAQ:RDHL) (Tel-Aviv Stock Exchange:RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on late clinical-stage development and commercialization of proprietary drugs for gastrointestinal diseases and cancer, reported that business update of its main activities and key highlights expected in 2018, including two Phase III readouts (Press release, RedHill Biopharma, APR 9, 2018, View Source [SID1234525807]).

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Key Highlights:

Top-line results from the ongoing Phase III study with RHB-104 for Crohn’s disease (MAP US study) are expected in mid-2018. Enrollment of all 331 subjects in the study has been completed and the last patient to reach the primary endpoint assessment (remission at week 26) is expected by early May 2018.

Top-line results from the ongoing confirmatory Phase III study with TALICIA (RHB-105)1 for H. pylori infection (ERADICATE Hp 2 study) are expected in H2/2018. To date, approximately 60% out of a planned total of 444 subjects have been enrolled in the study. TALICIA was previously granted QIDP fast-track designation by the FDA, including an extended market exclusivity period, if approved.

Amendment to RHB-106 agreement with Salix Pharmaceuticals. RedHill and Salix recently amended their 2014 worldwide license agreement relating to the
RHB-106 encapsulated bowel cleanser, as well as additional related rights. The amendment clarifies the development efforts to be used by Salix, as well as provides for enhanced involvement by RedHill in certain intellectual property matters. In addition, the parties have agreed to increase the lower end of the range of royalty payments to be paid to RedHill on net sales from low single digits to high single digits, such that the potential royalties now range from high single digits up to low double digits. Milestone payments remain unchanged.

Expected continued quarterly revenue growth. Net revenues in the fourth quarter of 2017 were $2 million, an increase of 31% over the third quarter of 2017. RedHill expects continued quarter over quarter net revenue growth. RedHill’s sales force of approximately 40 sales representatives is calling on thousands of gastroenterologists across the U.S.

Continued cost reduction in 2018. Cash to be used in operating activities is expected to continue to gradually decrease on average to approximately $8.5 million per quarter during 2018. RedHill’s cash position was approximately $46 million at the end of 2017, with no debt.
Additional Updates:

First five patients enrolled in the single-arm Phase IIa study with YELIVA (ABC294640) for the treatment of cholangiocarcinoma (bile duct cancer); Enrollment is expected to be completed by the end of 2018. The Phase IIa study was recently initiated at Mayo Clinic major campuses in Arizona and Minnesota, University of Texas MD Anderson Cancer Center and the Huntsman Cancer Institute, University of Utah Health, and is planned to enroll up to 39 patients. YELIVA was granted Orphan Drug designation by the FDA for the treatment of cholangiocarcinoma.

Ongoing discussions with the FDA on planned Phase III development programs for BEKINDA (RHB-102) for acute gastroenteritis and for IBS-D. Following the positive results of the Phase III study with BEKINDA 24 mg for acute gastroenteritis (GUARD study) and guidance provided by the FDA, RedHill is currently in discussions with the FDA on the design of a confirmatory Phase III study to support a potential New Drug Application (NDA). Following positive results of the Phase II study with BEKINDA 12 mg for IBS-D, RedHill plans to meet with the FDA in the second quarter of 2018 to discuss the design for one or two pivotal Phase III studies.

A pivotal Phase III study with RHB-104 for the treatment of nontuberculous mycobacteria (NTM) infections (QIDP fast-track designation, including an extended market exclusivity period, if approved) is expected to be initiated in H2/2018, subject to completion of a supportive non-clinical program and additional input from the FDA. RHB-104 is planned to be assessed as a first-line treatment of NTM disease caused by mycobacterium avium complex (MAC) infection.

Innovation Pharmaceuticals Phase 2 Oral Mucositis Trial Additional Data Show Brilacidin-OM Demonstrated A Significant Reduction in the Incidence of Severe Oral Mucositis in Patients with Head and Neck Cancer (HNC) Receiving Aggressive Chemotherapy Regimen

On April 9, 2018 Innovation Pharmaceuticals, (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, reported that further data analysis from its successfully completed Phase 2 clinical trial of Brilacidin-OM (see NCT02324335) for the indication of decreasing the incidence of Severe Oral Mucositis (SOM) in Head and Neck Cancer (HNC) patients receiving chemoradiation (Press release, Innovation Pharmaceuticals, APR 9, 2018, View Source [SID1234525806]).

Brilacidin-OM Subgroup Analysis (by Chemotherapy Regimen)

Brilacidin-OM was more effective in decreasing the incidence of SOM in HNC patients receiving the more aggressive chemotherapy regimen—cisplatin administered in a higher concentration (80-100 mg/m2), every 21 days—as compared to lower concentrations of cisplatin (30-40 mg/m2) administered weekly.

For the Modified Intent-to-Treat (mITT) population, Brilacidin-OM in the aggressive chemotherapy regimen reduced the incidence of SOM by 65.0% ([incidence control- incidence active]/incidence control) as compared with placebo (Brilacidin: 25.0%; placebo: 71.4%; p=0.0480). For the Per Protocol (PP) population, Brilacidin-OM in the aggressive chemotherapy regimen similarly reduced the incidence of SOM by 80.3% as compared with placebo (Brilacidin: 14.3%; placebo: 72.7%; p=0.0249). Treatments appeared well-tolerated with good safety.

These data, with additional analysis forthcoming based on the Clinical Study Report, further support Brilacidin’s potential as a promising, and clearly differentiated, late-stage OM drug candidate and will help inform the planning and design of future trials. Brilacidin-OM is being developed under FDA Fast Track Designation.

"We are delighted to see Brilacidin-OM demonstrate such high, statistically significant efficacy in patients receiving aggressive treatment for HNC," said Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "Reducing incidence of SOM sets the gold standard and is key to capturing the large HNC market currently lacking any approved drugs. With this new expanded information on the effectiveness of Brilacidin-OM, coupled with our previously reported successful primary results, we think our novel compound continues to raise the bar as the leading SOM drug in development."

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ONCOLOGY VENTURE SWEDEN AB: ONCOLOGY VENTURE EXERCISES OPTION TO IN-LICENSE DOVITINIB A PHASE 3 MULTI TYROSINE KINASE INHIBITOR

On April 9, 2018 Oncology Venture AB (OV:ST) ("OV" or the "Company") reported that it has entered into an agreement with Novartis Pharma AG (Basel, Switzerland) for the exclusive global rights to develop and commercialize dovitinib (TKI258), a small molecule, multi- tyrosine kinase inhibitor (TKI) (Press release, Oncology Venture, SEP 9, 2018, View Source [SID1234525604]). Novartis will receive an upfront payment, development milestones, and royalties on sales. Today’s announcement follows on an earlier agreement between the companies, that included an option for OV to in-license dovitinib at predetermined conditions. As part of the agreement, Novartis will be issued a convertible debt-to-equity note in a spinout company that OV has created to advance clinical development of the drug. Further terms of the agreement were not disclosed. In a Phase 3 trial in metastatic renal cell carcinoma, dovitinib achieved therapeutic equivalence with the current standard of care, sorafenib. Earlier stage studies explored its potential utility in multiple therapeutic indications including liver cancer, breast cancer and various solid tumors. OV intends to advance the compound in clinical trials together with a validated, drug-specific DRP biomarker as a companion diagnostic.

"Dovitinib has demonstrated clinically relevant efficacy in renal cancer and breast cancer and good efficacy in several other solid tumors, and we are excited to accelerate the development of the compound. We are confident that, by using our Drug Response Predictor (DRP) biomarker for dovitinib to select likely responder patients – and the recent success with a combination of a TKI and a PD-1 inhibitor (Keytruda) in renal cancer – we will raise the chances of success for dovitinib in further clinical development. The Dovitinib DRP biomarker could then be consequentially filed together with the Marketing Authorisation Application and used as a predictive companion diagnostic to select likely responders," said Peter Buhl Jensen, M.D., CEO of Oncology Venture.

During the prior option period, OV validated its proprietary DRP biomarker for the compound against anonymized biopsy data from the Novartis Phase 3 renal cancer study. A consistent signal was seen indicative of this biomarker’s ability to predict clinical benefit of dovitinib.

Under the global license agreement, OV will further refine the Dovitinib DRP biomarker to hone its predictive ability by analyzing data from additional biopsies and genomic data sets from other previous, relevant clinical studies with this promising compound. Dovitinib DRP will then be used to prospectively select patients most likely to respond to the compound for inclusion in a planned Phase 2 trial of the drug for the treatment of breast and liver cancer.

Oncology Venture recently announced positive interim results from another DRP-guided oncology program. In a prospective Phase 1/2 study of LiPlaCis (a targeted liposomal formulation of cisplatin) in heavily pre-treated breast cancer patients, in which enrollment was guided by the LiPlaCis DRP biomarker, clinical benefit was shown in 7 out of 10 evaluable patients. By comparison, conventional cisplatin treatment of metastatic breast cancer has reported a response rate of only 10 percent in previously conducted trials. This suggests that the LiPlaCis DRP successfully identified likely responders for inclusion into the clinical trial.

For further information, please contact

Ulla Hald Buhl, COO and Chief IR & CommunicationsMobile: +45 2170 1049E-mail: [email protected] Or Peter Buhl Jensen, CEOMobile: +45 21 60 89 22E-mail: [email protected]
About the Drug Response Predictor – DRP Companion Diagnostic

Oncology Venture uses the Medical Prognosis Institute (MPI) multi gene DRP to select those patients who by the genetic signature of their cancer are found to have a high likelihood of responding to the drug. The goal is developing the drug for the right patients, and by screening patients before treatment the response rate can be significantly increased. The DRP method builds on the comparison of sensitive vs. resistant human cancer cell lines, including genomic information from cell lines combined with clinical tumor biology and clinical correlates in a systems biology network. DRP is based on messenger RNA from the patient’s biopsies.

The DRP platform, i.e. the DRP and the PRP tools, can be used in all cancer types and is patented for more than 70 anti-cancer drugs in the US. The PRP is used by MPI for Personalized Medicine. The DRP is used by Oncology Venture for drug development

Allogene Therapeutics Completes Agreement for Pfizer’s Allogeneic CAR T Immuno-oncology Portfolio

On April 9, 2018 Allogene Therapeutics, Inc. (Allogene) reported the completion of the previously announced transaction between Pfizer Inc. (NYSE: PFE) and Allogene for Pfizer’s portfolio of assets related to allogeneic chimeric antigen receptor T cell (CAR T) therapy, an investigational immune cell therapy approach to treating cancer (Press release, Cellectis, APR 9, 2018, View Source [SID1234525478]).

On April 3, 2018, Allogene and Pfizer announced that the companies had entered into a definitive asset contribution agreement for Pfizer’s allogeneic CAR T portfolio. As a result of the completed agreement, Allogene has received from Pfizer the rights to 16 preclinical CAR T assets licensed from Cellectis and Servier and one clinical asset licensed from Servier, UCART19, an allogeneic CAR T therapy that is being developed for treatment of CD19-‐ expressing hematological malignancies. In partnership with Servier, UCART19 is initially being developed in acute lymphoblastic leukemia (ALL) and is currently in Phase I. UCART19 utilizes TALEN gene editing technology pioneered and owned by Cellectis.

With the agreement completed, Allogene is well-‐positioned to rapidly advance the portfolio of CAR T assets contributed by Pfizer into potential innovative new therapies, and ultimately to reach patients in need more quickly. "The completion of our agreement with Pfizer represents a bold undertaking by leaders in the field to expedite the development of the next wave of cancer immunotherapies," said David Chang, M.D., Ph.D., President and Chief Executive Officer of Allogene.

Pfizer will continue to participate financially in the CAR T portfolio’s development through a 25 percent ownership stake in Allogene. Prior to the agreement completion, Gilead Sciences joined Allogene’s premier Series A investment consortium that already included TPG, Vida Ventures, BellCo Capital, the University of California Office of the Chief Investment Officer, and Pfizer, among others.

Centerview Partners acted as financial advisor to Pfizer, with Ropes & Gray LLP acting as its legal advisor. Cooley LLP served as legal counsel to Allogene, Vida Venture and TPG. Gibson Dunn & Crutcher LLP also served as legal counsel to TPG.

Tiziana Life Sciences Announces a Poster Presentation on Phase II clinical data with Milciclib in Thymic carcinoma and Thymoma patients at the American Society of Clinical Oncology (ASCO) Meeting (June 1-5, Chicago IL)

On April 9, 2018 Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology company developing targeted drugs for cancer and inflammatory diseases, reported that clinical safety and efficacy data from two phase II clinical trials evaluating treatment of thymic carcinoma and thymoma patients with milciclib will be presented at the ASCO (Free ASCO Whitepaper) on June 1-5, 2018 in Chicago IL (Press release, Tiziana Life Sciences, APR 9, 2018, View Source [SID1234525410]). In these studies, milciclib, a small molecular pan-inhibitor of cyclin dependent kinases ("CDKs") met primary and secondary endpoints of the studies. The treatment regimen with milciclib (150mg/day; 7days On/7days Off) was safe and well-tolerated with some patients continuing therapy of up to 5 years.

The presentation, "Efficacy of milciclib (PHA-848125AC), a pan-cyclin d-dependent kinase inhibitor, in two phase II studies with thymic carcinoma (TC) and B3 thymoma (B3T) patients" will be given in the "Lung Cancer-Non-Small Cell Local-regional/Small Cell/Other Thoracic Cancers" session on June 3, 2018 from 4:45 PM to 6:00 PM by the principal author and investigator, Benjamin Besse, M.D., Institut Gustave Roussy, Villejuif France. Other investigators and authors of the study include Marina Chiara Garassino, M.D., Arun Rajan, M.D , Silvia Novello, M.D., Ph.D. , Julien Mazieres, M.D., Ph.D , Glen J. Weiss, M.D., Darren Kocs, M.D., Mark Barnett, M.D. , Cristina Davite, PhD. , Patrizia Crivori, Ph.D. and Giuseppe Giaccone, M.D, Ph.D.

MAJOR HIGHLIGHTS OF THE CLINICAL DATA
Milciclib was efficacious and met progression free survival ("PFS") as the primary endpoint and overall survival ("OS") as a secondary endpoint in two separate phase II multi-centered clinical trials (CDKO-125A-006: 72 patients and CDKO-125A-007: 30 patients) in patients with thymic carcinoma (TC) and thymoma (B3T) conducted in the USA, France and Italy.

Thymic carcinoma is an aggressive metastatic malignancy which is generally recognized as being more difficult to treat than thymoma. Milciclib treatment met primary endpoint PFS-3 (34.6 % and 53.8 %) and secondary endpoint OS (23.79 and 17.94 months) in these clinical studies.

The Disease Control Rate (DCR), defined as the percentage of patients with Stable Disease (SD), Complete Response (CR) and Partial Response (PR) in evaluable patients of TC was 69.2% in both trials. The DCR in evaluable B3T patients was 80.0% and 70.6% in CDKO-125a-006 and CDKO-125a-007, respectively.

Seven patients (5 patients in the CDKO-125A-006 study and 2 patients in the CDKO-125A-007) have been continuing treatment with Milciclib for more than 2 years with excellent safety profile. Among these, 2 patients have been treated with Milciclib for approximately 5 years, demonstrating safety of the drug for long term treatment.
"Thymic carcinoma and thymoma are unmet medical needs with no approved therapies. Particularly, it is very exciting that milciclib treatment was also efficacious in TC, which is an aggressive and difficult to treat metastatic cancer" Gabriele Cerrone, Chairman of Tiziana Life Sciences, commented.

"Demonstration of safety and efficacy in these two phase II clinical studies in patients with TC and B3T is a major milestone in clinical development of milciclib. We will work with regulatory agencies in US and Europe to develop plans to bring these first-in-class therapies to patients in need as soon as possible" said Kunwar Shailubhai, CEO & CSO of Tiziana Life Sciences.

About Thymic Carcinoma and Thymoma

Thymomas and thymic carcinomas are thymus tumors of epithelial origin. The incidence of thymic malignancies is approximately 1.5% of all malignancies with an overall incidence of 0.15 cases per 100,000. Thymic carcinomas are invasive and represent 0.06% of all thymic cancers, whereas thymomas tend to recur locally and are less likely to metastasize.(View Source).

About Milciclib

Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases such as CDK1, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signaling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. In a phase I study, oral treatment with Milciclib was found to be well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in NSCLC, Pancreatic and colon cancer, thymic carcinoma and thymoma.