On December 12, 2017 Cyclenium reported the signing of a drug discovery collaboration agreement with Ono Pharmaceutical Co., Ltd., a leading Japanese pharmaceutical research and development company (Press release, Cyclenium, DEC 12, 2017, View Source [SID1234635926]). The collaboration will exploit Cyclenium’s proprietary QUEST Library of next generation synthetic small-molecule macrocycles and associated optimization expertise to identify clinical candidates effective against multiple pharmacological targets selected by Ono in their therapeutic focus areas.

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While Cyclenium will be responsible for all medicinal chemistry efforts, starting from hit validation, to generate new macrocyclic compounds by employing its CMRTTM Technology, Ono will utilize its internal resources for the characterization of biological and pharmacological properties of these new macrocycles, as well as having full rights and responsibility for development and commercialization of the resulting drug candidates worldwide. In return, Cyclenium will receive an upfront payment and research funding from Ono, as well as development milestones and royalties on marketed products.

"We are very excited about entering this collaboration with Ono, our second with a major, globallyoperating, Japanese pharmaceutical partner," stated Helmut Thomas, Ph.D., President, Chief Executive Officer & Chief Scientific Officer of Cyclenium. "We are confident that our CMRT Technology and proven success in the macrocycle area combined with the excellent research team at Ono will provide new insight into the modulation of their difficult targets and enable the discovery of novel macrocyclic therapeutic agents."

"We highly appreciate Cyclenium’s expertise in the macrocycle area and their technology platform to generate new drug candidates for high priority targets in our portfolio," said Hiromu Habashita, Ph.D., Corporate Officer and Executive Director, Discovery and Research of Ono. "We are very pleased to work with Cyclenium on identifying and developing the next generation of innovative drugs and we believe novel macrocyclic drugs to be generated through this collaboration will fulfill unmet medical needs."

Cyclenium has translated its over 18 years of pioneering experience, extensive knowledge base and unparalleled expertise in small molecule macrocyclic chemistry into the next generation CMRT ("smart") drug discovery technology that addresses the shortcomings of earlier efforts in this increasingly important domain.

On December 11, 2017 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported the presentation of comprehensive dose-ranging data from two Phase 1b/2 studies of ALXN1210, the Company’s investigational long-acting C5 complement inhibitor, in patients with paroxysmal nocturnal hemoglobinuria (PNH), a chronic, progressive, debilitating and potentially life-threatening ultra-rare blood disorder characterized by complement-mediated hemolysis.1,2 Treatment with ALXN1210 for up to eight months resulted in rapid and sustained reduction of plasma lactate dehydrogenase (LDH) levels, a direct marker of hemolysis, with reductions in mean LDH levels from Baseline (BL) ranging from 73% to 88%. ALXN1210 was generally well tolerated with a safety profile that is consistent with that seen historically in patients with complement inhibition (Press release, Alexion, DEC 11, 2017, View Source [SID1234522523]). The data were presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in Atlanta. All patients from the Phase 1b study and from Cohorts 1, 2, and 3 of the Phase 2 study have been successfully transitioned to the Phase 3 dosing regimen, after which plasma LDH levels have remained suppressed.

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"It is encouraging to see rapid and sustained reduction in plasma LDH levels in these dose optimization studies," said Alexander Röth, M.D. from the Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany and an investigator in the Phase 1b/2 studies. "These comprehensive results provide robust preliminary evidence for the efficacy and safety of ALXN1210 as a future treatment for patients with PNH."

"The strength of these data and exposure-response analyses, along with the totality of data for ALXN1210 and discussions with global regulators, allowed us to determine an eight-week, weight-based dosing regimen that targets complete C5 inhibition and rapid and sustained suppression of LDH," said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. "We have completed enrollment in our two multinational Phase 3 PNH studies, with nearly 450 patients enrolled, and expect data from these studies in the second quarter of 2018."

Optimization of Dose Regimen for ALXN1210, a Novel Complement C5 Inhibitor, in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Results of Two Phase 1b/2 Studies 3

The researchers presented results from two open-label Phase 1b/2 studies designed to provide dose ranging data to optimize the dosing regimen for the Phase 3 development of ALXN1210 as a treatment for patients with PNH based on exposure-response assessments. The studies included a total of 39 adult patients with PNH (Study 103, n=13; Study 201, n=26) who were naïve to complement inhibition. The primary efficacy endpoint was the change from BL in mean plasma LDH levels to day 169 in Study 103 and day 253 in Study 201. The secondary efficacy endpoints were changes from BL in free hemoglobin, haptoglobin, and reticulocytes. Post hoc efficacy analyses evaluated the proportion of patients achieving LDH levels within the normal range and the incidence of breakthrough hemolysis (days 29-253). LDH BL was defined as the average of values at screening, prior to the first ALXN1210 infusion. For other parameters, BL was defined as the most recent value prior to the first infusion. Study 103 evaluated two escalating intravenous (IV) dosing regimens of ALXN1210, and Study 201 evaluated four IV regimens with different doses and intervals. The results demonstrated exposure-response relationships, and further substantiate and extend previously presented results.4,5,6,7

Study 201 Study 103
LDH at Protocol-Specified Endpointa Cohort 1
1000 mg q4w
n=6
Cohort 2
1600 mg q6w
n=6
Cohort 3
2400 mg q8w
n=7
Cohort 4
5400 mg q12w
n=7
Cohort 1
900 mg q4w
n=6
Cohort 2
1800 mg q4w
n=7
% LDH reduction from BL, mean (SD)b 72.9 (12.1) 77.8 (6.5) 85.0 (4.4) 87.6 (6.9) 86.0 (3.2) 84.7 (3.8)
LDH levels, U/L, mean (SD) 230.0 (44.0) 266.0 (54.3) 306.1 (130.7) 276.4 (196.9) 232.0 (82.3) 227.9 (50.6)
LDH normalization (D29-D253)c
LDH normalized, n/N (%) 5/6 (83) 3/6 (50) 4/7 (57) 5/7 (71) 4/6 (67) 6/7 (86)
LDH >1.5 x ULN, n/N (%) 4/6 (67) 3/6 (50) 2/7 (29) 3/7(43) 2/6 (33) 1/7 (14)
LDH >2 x ULN, n/N (%) 2/6 (33) 1/6 (17) 2/7 (29) 1/7 (14) 1/6 (17) 0/7 (0)
Breakthrough hemolysis (D29-253)d
Incidence of breakthrough hemolysis through day 253, n/N (%) 2/6 (33.3) 1/6 (16.7) 2/7 (28.6) 1/7 (14.3) 1/6 (16.7) 0/7 (0)
BL: baseline; SD: standard deviation; D: day; LDH: lactate dehydrogenase; ULN: upper limit of normal
q4w: every 4 weeks; q6w: every 6 weeks; q8w: every 8 weeks; q12w: every 12 weeks
a LDH parameters at protocol-specified endpoint: Study 103, day 169/24 weeks; Study 201, day 253/36 weeks.
b Primary efficacy endpoint.
c Patients meeting each parameter at least once after day 29 through day 253.
d Defined as at least 1 symptom or sign of intravascular hemolysis (fatigue, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL and hemoglobin< baseline hemoglobin], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) within ±7 days of an elevated LDH ≥2 x ULN after prior LDH reduction to <1.5 x ULN on therapy.

The most frequent related treatment-emergent adverse event (TEAE) was headache. No patient stopped treatment or withdrew from the studies, and there were no deaths. Two patients in Study 201 experienced meningococcal infections but recovered completely and continued receiving ALXN1210. Meningococcal infections are a known risk with terminal complement inhibition, and specific risk-management plans have been in place for ten years for Soliris (eculizumab) to minimize the risk for patients.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating and potentially life-threatening ultra-rare blood disorder that can strike men and women of all races, backgrounds, and ages without warning, with an average age of onset in the early 30s.1,2,8 PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.2 In patients with PNH, chronic, uncontrolled activation of the complement system, a component of the body’s immune system, results in hemolysis (the destruction of red blood cells)9, which in turn can result in progressive anemia, fatigue, dark urine and shortness of breath.10,11,12 The most devastating consequence of chronic hemolysis is thrombosis (the formation of blood clots), which can damage vital organs and cause premature death.13 Historically, it had been estimated that one in three patients with PNH did not survive more than five years from the time of diagnosis.2 PNH is more common among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).14,15,16 In certain patients with thrombosis of unknown origin, PNH may be an underlying cause.9

About ALXN1210

ALXN1210 is an innovative, long-acting C5 inhibitor discovered and developed by Alexion that works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system that, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). In early studies, ALXN1210 demonstrated rapid, complete, and sustained reduction of free C5 levels, as well as rapid and sustained reduction of plasma lactate dehydrogenase (LDH) levels, a direct marker of hemolysis (the destruction of red blood cells).4,5,6,7 ALXN1210 is currently being evaluated in Phase 3 clinical studies as a potential treatment for patients PNH and aHUS, administered intravenously every eight weeks. In addition, Alexion plans to initiate a single, pharmacokinetics (PK)-based Phase 3 clinical study of ALXN1210 delivered subcutaneously once per week as a potential treatment for patients with PNH and aHUS.

ALXN1210 has received Orphan Drug Designation (ODD) for the intravenous treatment of patients with PNH in the U.S. and EU, and for the subcutaneous treatment of patients with aHUS in the U.S.

About Soliris (eculizumab)

Soliris is a first-in-class complement inhibitor that works by inhibiting the C5 protein in the terminal part of the complement cascade, a part of the immune system that, when activated in an uncontrolled manner, plays a role in severe rare and ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). Soliris is approved in the U.S., EU, Japan, and other countries as the first and only treatment for patients with PNH and aHUS, in the EU as the first and only treatment of refractory generalized MG (gMG) in adults who are anti-AchR antibody-positive, and in the U.S. for the treatment of adult patients with gMG who are anti-AchR antibody-positive. Alexion’s new drug application in Japan for Soliris as a treatment for patients with anti-AchR antibody-positive refractory gMG has been accepted for review by the Japanese Ministry of Health, Labour, and Welfare (MHLW). Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS).

Soliris has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S., EU, Japan, and many other countries, for the treatment of patients with aHUS in the U.S., EU, and many other countries, for the treatment of patients with MG in the U.S. and EU, and for the treatment of patients with refractory gMG in Japan. Alexion and Soliris have received some of the pharmaceutical industry’s highest honors for the medical innovation in complement inhibition: the Prix Galien USA (2008, Best Biotechnology Product) and France (2009, Rare Disease Treatment).

For more information on Soliris, please see full prescribing information for Soliris, including BOXED WARNING regarding risk of serious meningococcal infection, available at www.soliris.net

Important Soliris Safety Information

The U.S. prescribing information for Soliris includes the following warnings and precautions: Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Comply with the most current Centers for Disease Control (CDC)’s Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Immunize patients with meningococcal vaccines at least two weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected. Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Patients may have increased susceptibility to infections, especially with encapsulated bacteria. Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenza type b (Hib). Soliris treatment of patients with PNH should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions.

In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis, back pain and nausea. In patients with aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, and pyrexia. In patients with gMG who are anti-AchR antibody-positive, the most frequently reported adverse reaction observed with Soliris treatment in the placebo-controlled clinical study (≥10%) was musculoskeletal pain.

On December 11, 2017 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") reported the first data of the investigational agent gilteritinib from the ongoing, open-label, dose escalation/expansion Phase 1 study (NCT02236013) in newly diagnosed patients with acute myeloid leukemia (AML) (Press release, Astellas Pharma US, DEC 11, 2017, View Source [SID1234522546]). The data are being presented today in an oral presentation at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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"These initial data shed encouraging light on the safety and tolerability of gilteritinib when combined with intensive chemotherapy for newly diagnosed AML patients," said Keith W. Pratz, M.D., of John Hopkins Sidney Kimmel Comprehensive Cancer Center, who is the principal investigator for the study. "In addition, while evaluating antitumor effects is an exploratory goal, the response rates in FLT3mut+ patients are promising and warrant expanded investigation of gilteritinib in this upfront treatment setting. Continuing research to evaluate the potential role for a FLT3 inhibitor in newly diagnosed patients and other stages of AML should continue to be a priority in our collective efforts to improve outcomes for patients."

The primary objective of this Phase 1 study is to assess the safety/tolerability profile, including dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD), of gilteritinib when combined with 7+3 induction (cytarabine and idarubicin) and high-dose cytarabine (HiDAC) consolidation chemotherapy, followed by single agent maintenance therapy in patients 18 years of age and older who have been newly diagnosed with AML. Assessment of antitumor effects of this combination therapy is an exploratory objective.

The two-part trial first enrolled patients to successive cohorts to determine the MTD. Successive cohorts received gilteritinib doses of 40, 80 or 120 mg/day. Dose escalation decisions were made based on DLTs that occurred following the first dose of gilteritinib during induction. Patients in the dose expansion cohort received gilteritinib at the recommended expansion dose established during dose escalation. Patients also received gilteritinib during consolidation, and then received maintenance therapy with once-daily gilteritinib over a 28-day cycle for up to 26 cycles.

"We are very encouraged by this initial data from our ongoing study of gilteritinib in combination with intensive chemotherapy in newly diagnosed AML patients, and pleased that it earned selection for oral presentation at ASH (Free ASH Whitepaper)," said Steven Benner, M.D., senior vice president and global therapeutic area head, Oncology Development, Astellas. "Mutations of FLT3 in AML are associated with a poor prognosis across the course of disease treatment and, through our comprehensive clinical development program, Astellas is committed to understanding how selective inhibition by gilteritinib might be beneficial to as many patients as possible."

As of July 9, 2017, 50 patients (n=17, dose escalation cohort; n=33, dose expansion cohort) had been enrolled in this ongoing study and 49 had received at least one dose of gilteritinib. Of the 48 patients with documented FLT3 mutation status, 23 (47.9%) were FLT3mut+, of whom 13 (56.5%) had internal tandem duplications (ITD).

Additional key findings include:

During dose escalation, two subjects in the 40 mg/day cohort who had received gilteritinib on days 1-14 experienced DLTs (neutropenia, thrombocytopenia and decreased ejection fraction). After gilteritinib induction schedule modification, no additional DLTs were observed.
The maximum tolerated dose was not reached; gilteritinib 120 mg/day was chosen as the recommended expansion dose.
Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurring in ≥ 10% of subjects were febrile neutropenia (36.7%), thrombocytopenia (18.4%), neutropenia (16.3%) and decreased platelet count (12.2%).
Serious drug-related TEAEs occurring in >1 subject were febrile neutropenia (n=8), sepsis (n=2), small intestinal obstruction (n=2), lung infection (n=2), and decreased ejection fraction (n=2).
In FLT3mut+ and FLT3 wild type subjects, end-of-treatment CRc rates were 100% and 60.9%, respectively.
About Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a cancer that impacts the blood and bone marrow, and its incidence increases with age. The American Cancer Society estimates that in 2017, approximately 21,000 new patients will be diagnosed with AML in the United States and about 10,000 cases will result in death.

About Gilteritinib

Gilteritinib is an investigational compound that has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) as well as FLT3 tyrosine kinase domain (TKD), two common types of FLT3 mutations that are seen in approximately one-third of patients with AML. Further, gilteritinib has also demonstrated inhibition of the AXL receptor in AML cell lines, which has been reported to be associated with therapeutic resistance. Astellas is currently investigating gilteritinib in various AML patient populations through several additional Phase 3 trials. Visit d to learn more about ongoing gilteritinib clinical trials.

Gilteritinib was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize gilteritinib. Gilteritinib has been granted Orphan Drug designation and Fast Track designation by the U.S. FDA, and SAKIGAKE designation by the Japan Ministry of Health, Labor and Welfare.

The safety and efficacy of the agent discussed herein are under investigation and have not been established. There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated. Information about pharmaceutical products (including products currently in development), which is included in this press release are not intended to constitute an advertisement or medical advice.

On December 11, 2017 IMMUNOPRECISE ANTIBODIES LTD. (the "Company") (TSX VENTURE: IPA)(OTC PINK: IPATF) reported that it has signed a binding letter of intent with ModiQuest Research BV ("ModiQuest") whereby the Company has agreed to acquire all of the issued and outstanding shares of ModiQuest (the "Transaction") (Press release, ModiQuest Therapeutics, DEC 11, 2017, View Source [SID1234522558]).

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The Transaction continues to realize on the Board’s commitment to grow globally through strategic acquisitions. It allows IPA to become a single source provider of services across the full antibody discovery value chain (antigen design, hit generation, lead selection, lead optimization and lead characterization) and to offer the full spectrum of antibody production methodologies (library based technologies, hybridoma methods, transgenic animal based platforms and single B cell based technology). Furthermore, the acquisition enhances the Company’s capacity for generating human antibodies.

"In acquiring ModiQuest Research B.V., IPA becomes a leading integrated antibody solutions company with global reach," said Dr. James Kuo, Chairman, Interim President of the Company.

ModiQuest

ModiQuest is a privately held company based in Oss, The Netherlands that specializes in the generation of monoclonal antibodies against difficult target antigens. ModiQuest applies proprietary technologies to all aspects of the antibody discovery process in research and development, diagnostic and therapeutic applications. Using its proprietary ModiFuse (hybridoma electrofusion), ModiSelect (B-cell selection) and ModiPhage (phage display) technologies, ModiQuest can generate very large panels of monoclonal antibodies from various backgrounds including mouse, rat, rabbit, chicken, llama and human, as well as transgenic animals harboring the human antibody gene repertoire. ModiQuest serves clients in Europe, the US, Asia and Russia. During its year-ended 2016, ModiQuest had revenues of €2,009,374 (CAD $3,037,249) and earnings of €671,799 (CAD $1,015,451).

The Transaction is accretive in both revenue and earnings and brings additional scientific and management capacity.

Terms of Transaction with ModiQuest

Under the binding letter of intent, the Company and ModiQuest have agreed to negotiate a definitive agreement (the "Definitive Agreement") whereby the Company will acquire all of the issued and outstanding shares of ModiQuest for €7,000,000 (CAD$10,570,000) (the "Purchase Price"), of which (A) €2,500,000 (CAD$3,775,000) will be paid in cash on closing, (B) €2,500,000 (CAD$3,775,000) will be satisfied by the issuance of approximately 6,622,807 common shares of the Company on closing, and (C) €2,000,000 (CAD$3,020,000) in deferred payments over a three year period (the "Deferred Payments"). The Deferred Payments will be made in three equal installments of cash and equity totaling €666,666 (CAD$1,006,665) on each anniversary date following closing of the transaction. The Deferred Payments will be prorated if the EBITDA of ModiQuest fails to equal the average EBITDA from the previous two years. ImmunoPrecise expects to finance the cash portion of the purchase price using a convertible debt instrument.

The letter of intent also requires that Jos Raats, a principal of ModiQuest, to enter into a three year management contract, which will include non-solicitation and non-competition clauses, and Mr. Raats will provide a minimum of 60% of full time employment to ModiQuest under the management contract. The Company has also agreed to appoint one of the principal shareholders of ModiQuest to its board of directors.

The parties will be entitled to carry out due diligence of each other until February 15, 2018. Upon the parties completing due diligence to their reasonable satisfaction, the parties will enter into the Definitive Agreement setting forth the terms and conditions of the Transaction by February 28, 2018. Completion of any transaction with ModiQuest is subject to a number of conditions, including but not limited to, completion of due diligence, negotiation of definitive agreements in respect of such a transaction, the availability of financing on terms acceptable to the Company, and receipt of any required regulatory and shareholder approvals. A transaction cannot be completed until these conditions are satisfied, and there can be no assurance that a transaction will be completed at all.

On December 11, 2017 Innovation Pharmaceuticals, (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, reported successful topline results from the Company’s randomized, double-blind, placebo-controlled, Phase 2 clinical trial of Brilacidin (see NCT02324335) for the prevention and control of Oral Mucositis (OM) in patients receiving chemoradiation for treatment of Head and Neck Cancer (Press release, Innovation Pharmaceuticals, DEC 11, 2017, View Source [SID1234522527]). Brilacidin-OM is being developed under an FDA Fast Track designation for this indication.

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Summary of Topline Results from the Placebo-Controlled Phase 2 Trial

· Brilacidin met primary endpoint of reduced incidence of severe OM experienced by patients during radiation therapy.
· Incidence of severe OM in Modified Intent to Treat (mITT) Population: Brilacidin 42.9%, Placebo 60.0%.
· Incidence of severe OM in Per Protocol (PP) Population: Brilacidin 36.8%, Placebo 60.0%.
· Trial results support continued and expedited development of Brilacidin-OM.

Clinical Trial Background

In this trial, Head and Neck Cancer patients self-administered Brilacidin (45 mg/15 ml oral rinse—"swish and spit") or placebo three times daily across 7 consecutive weeks (49 days). Of the 61 patients randomized, 46 patients met the cumulative radiation dose criteria of at least 55 Gy—the minimum treatment threshold for inclusion in the efficacy population—and 39 of these patients met more strict criteria for inclusion in the "per protocol" study population. The trial’s primary endpoint was established as reduced incidence of severe OM (defined as Grade ≥ 3 on the WHO Oral Mucositis scale) experienced by patients during radiation therapy.

Topline results reveal a clear reduction in the incidence of severe OM (WHO Grade ≥ 3) in patients treated with Brilacidin-OM as compared to those on placebo. Brilacidin also appeared generally safe and well-tolerated across all treated patients (the safety population).

Primary Efficacy Results: Incidence of severe OM (WHO Grade ≥ 3)

Active (Brilacidin) Control (Placebo)

Modified Intent to Treat 9 of 21 patients (42.9 %) 15 of 25 patients (60.0%)
(mITT) Population (n=46)
Per Protocol
(PP) Population (n=39) 7 of 19 patients (36.8%) 12 of 20 patients (60.0%)

Overall reduction in observed severe Oral Mucositis (WHO Grade ≥ 3) in the Brilacidin-OM treatment group from that seen in the control group ([incidence control – incidence active]/incidence control) was: 28.5% (mITT population) and 38.7% (PP population).

Safety and Tolerability Profile

Brilacidin administered as an oral rinse was generally well-tolerated by patients. Safety findings were typical for patients with Head and Neck Cancer being treated with chemoradiation, with all treated patients reporting at least one Treatment-Emergent Adverse Event (TEAE). Of the TEAEs categorized as serious (SAEs), 13 patients (8 in the Brilacidin group, and 5 in the Placebo group) experienced at least one SAE. No SAEs reported led to death. None of the SAEs were classified by the Investigator as related to Brilacidin.

Management Comments

Additional study endpoint analyses are ongoing, with outputs expected in the coming weeks. These endpoints are important in building a deeper knowledge base around Brilacidin-OM, further informing other aspects of efficacy and helping to plan the next stage of clinical development.

"The completion of the Phase 2 trial of Brilacidin-OM is a major milestone for the Company, particularly given the successful topline study results. In a broader context, these mid-phase study results represent a watershed moment in the management of OM, as there has been negligible prior innovation in safely mitigating the onset of the severest stages of the disease," commented Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals. "We believe that we now occupy a leadership position with this drug candidate in the prevention and treatment of severe OM in Head and Neck Cancer patients. Considering the global unmet medical need in treating severe OM, we anticipate leveraging these promising data, both in securing potential partnership opportunities and establishing an early competitive market position. In combination with other promising clinical data on Brilacidin, we are building a strong case that our novel defensin-mimetic pipeline can safely address an array of diseases and conditions by showing meaningful clinical responses. We now look forward to discussing our plans with the FDA to best align and prepare for the expedient advancement of the Brilacidin-OM program."

"Based on these data, we are confident Brilacidin-OM has potential to improve significantly the treatment paradigm for OM," said Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "To see a clear beneficial clinical response is what clinicians hope for—a viable drug candidate bettering the lives of patients in dire need of newer treatment options. Further, today’s news is added validation of the Brilacidin Franchise, now anchored in three distinct clinical indications—OM, inflammatory bowel disease and serious skin infections. Brilacidin is an extremely unique drug candidate that we look forward to continuing to explore and advance across its many therapeutic applications."

About Brilacidin

Brilacidin is Innovation Pharmaceuticals’ lead drug candidate in its defensin mimetic franchise. Modeled after Host Defense Proteins (HDPs), the "front-line" of defense in the immune system, it is a small, non-peptidic, synthetic molecule that kills pathogens swiftly and thoroughly. Just as importantly, Brilacidin also functions in a robust immunomodulatory capacity, lessening inflammation and promoting healing. Due to its unique properties, the Company is studying Brilacidin’s effect on Oral Mucositis (under Fast Track designation) and on Ulcerative Proctitis / Proctosigmoiditis (UP/UPS) in Phase 2 trials. Additional trials of Brilacidin are planned in other conditions, including: Atopic Dermatitis, Hidradenitis Suppurativa and Acne. Brilacidin is also being developed under FDA’s Qualified Infectious Disease Product (QIDP) designation as an antibacterial product for Acute Bacterial Skin and Skin Structure Infection (ABSSSI)—qualifying it for Fast Track and possible Priority FDA Review and an extra 5 years of United States market exclusivity upon drug approval.

Learn more here:
View Source

About Brilacidin-OM

Innovation Pharmaceutical’s first-in-class immunomodulatory drug candidate, Brilacidin, targets the prevention of severe Oral Mucositis (OM)—a common and debilitating side-effect of receiving chemoradiation therapy—in Head and Neck Cancer. Each year, OM affects hundreds of thousands of patients worldwide. Only a limited number of OM treatments are available, most of which are palliative in nature. A Phase 2 randomized, placebo-controlled clinical trial of Brilacidin-OM (see NCT02324335) has been recently completed in which topline results demonstrate a reduced rate of severe OM (WHO Grade >3) in patients treated with Brilacidin-OM compared to those on placebo.

About Oral Mucositis

Oral Mucositis (OM) is a frequent, painful and debilitating complication of chemoradiation. Head and Neck Cancer (HNC) patients—comprising an estimated 65,000 newly diagnosed cases in the U.S. alone in 2017, and an estimated 700,000 worldwide (source: GLOBOCAN)—are at the greatest risk of developing OM (a 90 to 100 percent rate of occurrence). By 2030, the global incidence of HNC cases is expected to exceed 1 million per year. Moreover, between 25 and 60 percent of cancer patients, regardless of cancer type, also will experience OM. Characterized by inflammation and ulceration, patients suffering from OM are often unable to speak and eat (requiring the insertion of a feeding tube) and are more susceptible to infections, with severe cases leading to hospitalization at increased treatment costs of up to $25,000. There currently are no approved medications for the prevention of OM in the HNC population, with only limited palliative care options available. Worldwide, the potential market for OM is expected to exceed $1 billion in the next few years.