On April 16, 2018 Innovation Pharmaceuticals (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, is pleased to report additional information from the Company’s successfully completed Phase 2 clinical trial of Brilacidin-OM (see NCT02324335) for the indication of decreasing the incidence of Severe Oral Mucositis (SOM) (WHO Grade ≥3) in Head and Neck Cancer (HNC) patients receiving chemoradiation (Press release, CellCeutix, APR 16, 2018, View Source [SID1234525812]).

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These additional data align with previously released Brilacidin-OM results showing a risk reduction in the incidence of SOM, including up to an 80.3% risk reduction in the incidence of SOM among patients receiving more aggressive chemotherapy. Other previously released results indicate Brilacidin-OM also delayed onset of SOM. The Company is developing Brilacidin-OM under FDA Fast Track designation as a convenient, and clearly differentiated, therapy aimed to decrease incidence of SOM.
Initial Instance Duration of SOM was defined as the number of days from initial WHO Grade ≥3 during radiation therapy to the first WHO Grade 2 or lower OM Grade. Overall Duration of SOM was defined as the number of days from initial WHO Grade ≥3 during radiation therapy to the day prior to the next OM assessment after the last WHO Grade ≥3 during/after radiation therapy. Note: 50th percentiles are from Kaplan-Meier analysis. Patients who did not experience SOM have duration set to 0.

Previously, the Company reported statistically significant results showing Brilacidin-OM reduced the incidence of SOM in HNC patients receiving cisplatin administered in a high-dose regimen (80-100 mg/m2), approximately every 21 days. For the Modified Intent-to-Treat (mITT) population, Brilacidin-OM in the high-dose 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 high-dose chemotherapy regimen similarly reduced the incidence of SOM by 80.3% as compared with placebo (Brilacidin: 14.3%; placebo: 72.7%; p=0.0249).

Exploratory Endpoint: Unplanned Office Visits, Emergency Department Visits, and/or Hospital Admissions Due to OM

Positive OM assessment endpoints are additionally supported by zero (0) of the patients in the Brilacidin-OM group having unplanned office visits, ED visits, or hospital admissions due to OM, compared to four (4) patients in the placebo group.

Other Study Observations

Regardless of the oral sites irradiated (at least two sites from: buccal mucosa, floor of mouth, ventral/lateral tongue, and soft palate), the incidence by patient of Severe OM on Brilacidin-OM relative to placebo was consistently reduced.

Across cumulative radiation dose intervals, patients in the Brilacidin-OM group consistently reported less often feeling the sensation "swollen" (approximately half of that reported for the placebo group). "Burning" sensation also was reported consistently less frequently in the Brilacidin treatment group.

Patients in the Brilacidin-OM group appeared to trend more favorably over the course of chemoradiation treatment according to Eastern Cooperative Oncology Group (ECOG) Performance Status—a common set of criteria used in oncology trials to assess debility.

Management Comments

"Drug makers, the world-over, have spent decades and enormous sums in both money and resources trying to develop an effective OM drug in a bid to address dire patient needs as well as capture a tremendous market opportunity," commented Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals. "Yet, there is currently no drug approved to treat, let alone prevent, severe OM in patients with Head and Neck Cancer. Most Pharmas currently conducting OM trials target shortening the duration of severe OM as their primary endpoint, not reduction of incidence, like we did. The Brilacidin-OM Phase 2 trial met its primary objective and its key secondary objectives. As we continue to analyze subset data, we are extremely enthusiastic about observed trends. Hundreds of thousands of patients would benefit from a preventative OM treatment and we’re excited that Brilacidin-OM may one day provide these patients a much-needed breakthrough treatment option."

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On April 16, 2019 Phoenix Molecular Designs (PhoenixMD), a privately-held biotechnology company designing precise cancer therapeutics by targeting essential kinases, reported that it has entered into a collaboration with STA Pharmaceutical Co., Ltd (STA), a WuXi AppTec group company, to manufacture the PMD-026 needed for IND-enabling toxicology studies and a Phase I study in women (Press release, Phoenix Molecular Designs, APR 16, 2018, View Source [SID1234536961]).

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Under the terms of the collaboration agreement, STA will become a new manufacturing partner for PhoenixMD for their platform of kinase inhibitor drug candidates to treat a wide range of unmet medical needs, with an initial focus on triple negative breast cancer (TNBC). STA will be responsible for the early manufacturing work through their GMP-certified site in San Diego, CA. Through these collaborative efforts, PhoenixMD expects to file an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration (FDA) for PMD-026.

Dr. Minzhang Chen, CEO of STA, commented, "We are excited to manufacture PMD-026 and enable Phoenix MD to advance this novel RSK inhibitor to shrink tumors in Phase 1 studies in women."

"We’re thrilled to collaborate with STA, a global leader in drug development and manufacturing, who has helped us achieve an important milestone in the efficient and scalable manufacturing of PMD-026," said Sandra E. Dunn, CEO PhoenixMD. "Through this work, we have demonstrated that PMD-026 has the potential to be disease-modifying with its ability to block the RSK pathway signaling and initiating significant tumor shrinkage of up to 70% in TNBC xenograft models. Looking ahead, we expect to build upon this progress and file an IND for PMD-026, with the ultimate goal of confirming these revolutionary results in women suffering from TNBC."

Gerrit Los, CSO of PhoenixMD added, "It is critical to have a manufacturing partner at this stage of development for PMD-026. This collaboration will allow us to move PMD-026 into IND enabling toxicology studies and to get ready for a successful IND filing. Importantly, it provides us the security to have access to GMP quality API when we are ready to start our Phase I study."

About Triple Negative Breast Cancer (TNBC) and RSK Kinases

Approximately 400,000 cases of TNBC are diagnosed every year worldwide and it is one of the most difficult breast cancer subtypes to treat due to lack of effective, targeted therapies. TNBC also claims the lives of young women more than any other type of breast cancer due to a lack of understanding around the therapeutic bullseye. It is also a very heterogeneous disease, therefore a common denominator across TNBC types was necessary to identify the bullseye. Through genome-wide screens, RSK was identified as the prime target for TNBC by scientists at PhoenixMD. Currently, there are still no targeted therapies available for TNBC.

There are four types of RSK involved in cancer, known as RSK1-4, and each type has a unique role in the development of the disease. RSK1 is responsible for cancer cell invasion and is an important driver in the spread of cancer. RSK2 controls cancer cell growth, and RSK3 and RSK4 are associated with drug resistance.

RSK1 and RSK2 have been proven critical to the survival of patients with TNBC. Over 90% of primary TNBC express high levels of RSK1 and RSK2. Inhibiting RSK2 eliminates TNBC cells completely, including cancer stem cells, which give rise to cancer recurrence. PhoenixMD, with its novel, targeted approach, is focused on creating patented cancer RSK inhibitors and companion diagnostics for cancer indications – initially in breast cancer – with the potential to treat blood, brain, ovarian, lung, skin, prostate, colon, head and neck cancers.

Currently, there are no approved targeted therapies for TNBC, although several drugs are subject to research studies and clinical trials. PhoenixMD is addressing this unmet medical need through a novel, targeted approach by inhibiting critical kinases, such as RSK1-4, a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. For this target, PhoenixMD developed PMD-026, a first-in-class, specific RSK inhibitor that blocks downstream signaling of RSK and induces apoptosis.

On April 16, 2018 Oregon Health & Science University (OHSU) Knight Cancer Institute and Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG’806, a highly potent pan-FLT3/pan-BTK inhibitor, kills malignant cells in samples from patients with various hematologic malignancies and demonstrates superiority to other kinase inhibitors (Press release, Aptose Biosciences, APR 16, 2018, View Source c=116148&p=RssLanding&cat=news&id=2342649 [SID1234525328]). The data were presented in a poster on Sunday, April 15, at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference being held April 14-18, in Chicago, IL.

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The poster, entitled CG’806, a first-in-class pan-FLT3/pan-BTK inhibitor, demonstrates superiority to other FLT3 and BTK inhibitors against primary patient samples, demonstrated the broad activity of CG’806 against primary bone marrow specimens from patients with various hematologic malignancies. CG’806 is a small molecule that potently inhibits wild type (WT) FLT3, as well as FLT3 housing the ITD mutation or with point mutations in the tyrosine kinase domain (TKD, including D835G, D835Y, D835H) or in the gatekeeper region (F691L); it also inhibits BTK WT and BTK-C481S. As part of the Beat AML Initiative, researchers at OHSU tested CG’806 against freshly isolated primary samples from patients with acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and other hematologic malignancies to determine its potency and range of action. Against AML patient samples, CG’806 was evaluated relative to other FLT3 inhibitors. In parallel, CG’806 and ibrutinib, a covalent BTK inhibitor approved for CLL and certain other B-cell malignancies, were compared directly for sensitivities on primary CLL samples and various B-cell and other hematologic malignancies. CG’806 was shown to have greater potency against a broader subset of AML samples relative to other FLT3 inhibitors, including midostaurin, gilteritinib, quizartinib, sorafenib, crenolanib, and dovitinib. This was especially true in FLT3-ITD and FLT3-TKD positive cases, although enhanced activity was also observed in FLT3 WT samples. CG’806 was also shown to have greater potency and range of activity on primary CLL samples than ibrutinib.

"The clinical benefit of current FLT3 inhibitors in AML is transient, as resistance develops after several months of treatment," said Stephen E. Kurtz, Ph.D., lead author and Research Assistant Professor at the OHSU Knight Cancer Institute. "Similarly, ibrutinib, a covalent BTK inhibitor approved for CLL and certain other B-cell malignancies, is limited by acquired resistance, as well as refractory disease and tolerance challenges. As a pan-FLT3/pan-BTK inhibitor – especially in the absence of observed toxicity in murine AML models – CG’806 offers important potential to address these limitations."

"CG’806 appears superior to other FLT3 and BTK inhibitors, and the wealth of data supporting its development in AML and B-cell malignancies continues to grow," said William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "These studies are critical for understanding how to develop and position CG’806 as we prepare for clinical development in these challenging hematologic malignancies."
Separately, Aptose researchers also announced new data on CG’806 presented at AACR (Free AACR Whitepaper) (see press release here). Both poster presentations will be published in the AACR (Free AACR Whitepaper) Conference Proceedings. The posters can also be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.
For more information on Beat AML refer to View Source

About CG’806

CG‘806 is an oral, first-in-class pan-FLT3/pan-BTK multi-kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG’806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. CG’806 is currently in preclinical development in partnership with CrystalGenomics

On April 16, 2018 SELLAS Life Sciences Group Inc. (Nasdaq: SLS) ("SELLAS"), a clinical-stage biopharmaceutical company focused on novel cancer immunotherapies for a broad range of cancer indications, reported financial results for the year ended December 31, 2017 and provided a business update (Press release, Galena Biopharma, APR 16, 2018, View Source [SID1234525344]).

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"In recent months, we have made meaningful progress advancing our business objectives, maturing SELLAS Life Sciences Group Ltd. into a publicly-traded company following the business combination and progressing our pipeline of cancer immunotherapies for patients with limited treatment options," said Angelos Stergiou, MD, ScD h.c., President & Chief Executive Officer of SELLAS. "We are particularly excited about our recent financing and the positive interim results from the Phase 2b NeuVax + Herceptin study announced earlier this month which we believe help position SELLAS for continued success throughout the remainder of 2018. We also look forward to commencing the Phase 1/2 clinical trial of galinpepimut-S in combination with Keytruda under our collaboration and supply agreement with Merck and our planned Phase 3 Acute Myeloid Leukemia program."
Recent Corporate and Pipeline Highlights

In April 2018, SELLAS announced positive interim data from the prospective, randomized, single-blinded, controlled Phase 2b independent investigator-sponsored clinical trial (IST) of trastuzumab (Herceptin) +/-nelipepimut-S (NeuVax) in HER 1+/2+ breast cancer patients in the adjuvant setting to prevent recurrences.

In March 2018, open label Phase 2 clinical and immunological data for SELLAS’ lead product candidate, galinpepimut-S (GPS) in patients with multiple myeloma (MM) was presented at the 2018 European Society for Blood and Marrow Transplantation (EBMT) 44th Annual Meeting in Lisbon, Portugal. Median progression-free survival (PFS) of 23.6 months was reported in the high-risk disease setting, compared to historically inferior outcomes while on an immunomodulatory drug (IMID) or proteasome inhibitor post-autologous stem cell transplant maintenance.

In March 2018, SELLAS appointed Barbara Wood as Executive Vice President, General Counsel and Corporate Secretary.

In March 2018, SELLAS entered into a definitive securities purchase agreement to issue up to 10,700 shares of its Series A convertible preferred stock and warrants to purchase 1,363,631 shares of its common stock in a private placement transaction to a select group of institutional investors, in Europe and the United States, for aggregate gross proceeds of $10.7 million. The closing of the first tranche for approximately $6.0 million took place on March 9, 2018. The closing of the second tranche for approximately $4.7 million is expected to occur by the end of April 2018 following stockholder approval.

In December 2017, SELLAS Life Sciences Group Ltd. ("SELLAS Ltd."), a privately-held Bermuda exempted company, completed a business combination (the "Merger") with Galena Biopharma, Inc. ("Galena"). Upon completion of the Merger, Galena was renamed "SELLAS Life Sciences Group, Inc.," began trading under a new ticker symbol "SLS" and the combined company now includes the late-stage pipelines of novel cancer immunotherapies for both hematologic and solid malignancies of SELLAS Ltd. and Galena.

In October 2017, SELLAS Ltd. entered into a clinical trial collaboration and supply agreement with Merck & Co. for a combination clinical trial targeting multiple cancer types, in which GPS will be administered in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in a Phase 1/2 trial in five cancer indications, including both hematologic malignancies and solid tumors.

Year End 2017 Financial Results
For accounting purposes, SELLAS Ltd. is considered to have acquired Galena in the Merger; therefore, the financial statements of Galena became those of SELLAS Ltd. and the results reported are those of SELLAS Ltd.
Cash Position: As of December 31, 2017, cash and cash equivalents were $2.3 million, compared to $6.0 million as of December 31, 2016. Net cash used in operating activities was $11.0 million for the year ended December 31, 2017, compared to $11.9 million for the year ended December 31, 2016.
R&D Expenses: Research and development expenses were $6.1 million for the year ended December 31, 2017, as compared to $11.4 million for the year ended December 31, 2016. The $5.3 million decrease was primarily attributable to a decrease of $2.5 million in fees due under licensing and collaboration agreements, a decrease of $1.7 million in clinical trial expense, a $1.3 million decrease in manufacturing expenses, a $1.2 million decrease in consulting fees, and $0.2 million decrease in regulatory expenses. These decreases were partially offset by a $0.7 million increase in stock-based compensation and a $0.9 million increase in personnel related expenses. Overall, research and development expenses were reduced in 2017 as SELLAS Ltd. explored various strategic options.
G&A Expenses: General and administrative expenses were $15.1 million for the year ended December 31, 2017, as compared to $4.6 million for the year ended December 31, 2016. The $10.5 million increase was primarily due to $5.7 million of transaction costs related to the Merger and a $2.1 million increase in stock-based compensation from the acceleration of restricted stock units, and a $1.5 million increase in personnel related expenses due to an increase in headcount, $0.6 million increase in accounting and audit fees, and $0.6 million in outside consulting services. The $5.7 million of transactions costs consist of $2.9 million of banking fees, $1.6 million in legal fees, $1.0 million incentive fee payable through approximately $0.1 million in cash and the issuance of 119,672 shares of our common stock upon consummation, and $0.2 million in accounting and audit fees. The transaction costs incurred related to the Merger are non-recurring expenses for the year 2017.
Non-recurring Severance Costs: Severance costs incurred during the year ended December 31, 2017 include employee-related costs for severance of former Galena employees of $1.9 million.
Net Loss: Net loss was $23.8 million and loss attributable to common stockholders was $24.4 million for the year ended December 31, 2017, or a basic and diluted loss per share to common stockholders of $10.44, as compared to a net loss and loss attributable to common stockholders of $17.7 million for the year ended December 31, 2016, or a basic and diluted loss per share to common stock holders of $18.66.

On April 16, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of genes, reported new preclinical data showing that SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor currently in a Phase 1 trial in patients with advanced solid tumors, demonstrated potent anti-tumor activity in multiple models of heavily pretreated ovarian cancer (Press release, Syros Pharmaceuticals, APR 16, 2018, View Source [SID1234525362]). These data were presented by Syros and its collaborators from the Dana-Farber Cancer Institute (DCFI) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago.

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"Despite recent advances in treating ovarian cancer, many patients either don’t respond or become resistant to treatment, and the outlook for these patients is poor," said Panagiotis A. Konstantinopoulos, M.D, Ph.D., Director of Translational Research and attending oncologist in the Gynecologic Oncology Program at DCFI and an Associate Professor of Medicine at Harvard Medical School. "SY-1365 stopped tumor growth in multiple preclinical models of ovarian cancer that had progressed following treatment with standard-of-care and targeted therapies. These data suggest SY-1365 has the potential to be an important new therapy for ovarian cancer that warrants further clinical investigation."

Researchers from Syros and DCFI evaluated the anti-tumor activity of SY-1365 in a broad panel of ovarian cancer cell lines, as well as in patient-derived xenograft (PDX) mouse models developed from patients treated with multiple prior therapies, including standard-of-care platinum-based therapies and a new class of targeted therapies known as PARP inhibitors. The data, which were presented in a poster discussion session and a poster session, show that SY-1365:
Induced cell death in numerous ovarian cancer cell lines.
Inhibited tumor growth in 10 of the 17 treatment-relapsed ovarian PDX models studied, including inducing complete regressions. Notably, these responses were observed irrespective of BRCA status or sensitivity to a PARP inhibitor.
Lowered expression of MCL1, a gene in the mitochondrial apoptosis pathway that is known to inhibit apoptosis, or programmed cell death.

The data also showed that sensitivity to SY-1365 was associated with low expression of BCLXL, a known apoptosis inhibitor, and RB1, a known tumor suppressor, pointing to potential biomarkers that may be predictive of response to SY-1365.

"We are very encouraged by these data," said David A. Roth, M.D., Chief Medical Officer of Syros. "CDK7 has emerged as a potentially important new drug target in cancer. By selectively inhibiting CDK7, SY-1365 has been shown to lower the expression of cancer driving genes and hit cancer cells at multiple points in the cell cycle, preferentially killing cancer cells and inhibiting tumor growth in preclinical models of a number of difficult-to-treat solid tumors and blood cancers. These newest data in ovarian cancer provide strong support for the planned expansion of our Phase 1 clinical trial into ovarian cancer and further highlight the promise of SY-1365 to make a profound difference for patients."

The ongoing Phase 1 trial of SY-1365 is a multi-center, open-label trial enrolling patients with advanced solid tumors. The primary objective of the trial is to assess the safety and tolerability of escalating doses of SY-1365, with the goal of establishing a maximum tolerated dose and a recommended Phase 2 dose and regimen. The dose-escalation phase is open and expected to enroll approximately 35 solid tumor patients for whom standard curative or palliative measures do not exist or are no longer effective. Following the dose-escalation phase, Syros plans to open expansion cohorts to further evaluate the safety and anti-tumor activity of SY-1365 as a single agent and in combination with standard-of-care therapies in multiple ovarian and breast cancer populations.
Syros expects to open the expansion phase of the trial in mid-2018 and to report data from the dose escalation portion of the trial in the fourth quarter of 2018.
About SY-1365

SY-1365 is a first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor with potential across a range of difficult-to-treat solid tumors and blood cancers. In preclinical studies, SY-1365 has shown significant anti-proliferative and pro-apoptotic activity in difficult-to-treat cancers, including breast and ovarian cancers and acute leukemia. SY-1365 has also been shown to preferentially kill cancer cells over non-cancerous cells and lower the expression of cancer-driving genes, inducing significant anti-tumor activity, including complete tumor regressions, in preclinical models of these cancers. SY-1365 is currently in a Phase 1 clinical trial in patients with advanced solid tumors, with planned expansion cohorts to evaluate SY-1365 in multiple ovarian and breast cancer patient populations as a single agent and in combination with standard-of-care therapies. Additional details about the trial can be found using the identifier NCT03134638 at www.clinicaltrials.gov.