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MorphoSys Presents Updated Clinical Data for Anti-CD38 Antibody MOR202 in Multiple Myeloma at ASCO 2017

On June 5, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported safety and efficacy data from an ongoing phase 1/2a study of the anti-CD38 antibody MOR202 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting in Chicago (Press release, MorphoSys, JUN 5, 2017, View Source [SID1234519413]). The dose escalation trial comprises three arms: MOR202, MOR202 in combination with the immunomodulatory drug (IMiD) lenalidomide (LEN) and MOR202 in combination with the IMiD pomalidomide (POM), in each case with low-dose dexamethasone (DEX). The trial is being conducted in heavily pre-treated patients with relapsed/refractory multiple myeloma.

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"Antibodies directed against CD38 have been reported as a class of potential therapeutics for patients with relapsed or refractory multiple myeloma. Based on the maturing data generated for MOR202, we will intensify our evaluations to further develop this compound as a representative of this class," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "We are optimistic about the responses seen in patients treated with MOR202 plus LEN/DEX and POM/DEX as well as the relatively short infusion time and the occurrence of infusion-related reactions in a low proportion of patients observed. We look forward to results further maturing from patients treated in this ongoing trial and to presenting final data later this year."

MOR202 was given as a 2-hour infusion up to the highest dose of 16 mg/kg. Infusion-related reactions (IRRs) occurred in 6% of patients in the clinically relevant dose cohorts of MOR202 (4 mg/kg, 8 mg/kg, 16 mg/kg) and were limited to grade 1 or 2. The most frequent adverse events of grade 3 or higher were neutropenia, lymphopenia, and leukopenia in 42%, 40%, and 33% of patients respectively. No unexpected safety signals were observed.

Patients treated with MOR202 in combination with LEN/DEX had a median of three prior treatment regimens, 56% being refractory to at least one prior therapy. Median progression-free survival (PFS) was not yet reached, median follow-up was 7.5 months and 9 patients were still on study at data cut-off. 12 out of 17 patients (71%, based on the ITT population) reported an objective response (OR) to treatment, including one complete remission (CR), three very good partial responses (VGPR) and eight partial responses (PR).

Patients receiving MOR202 with POM/DEX, had a median of four prior treatment regimens, all being refractory to at least one prior therapy. Current median PFS is 17.5 months, with a median follow-up of 8.5 months. Eight patients were still on study at data cut-off. 6 out of 13 patients (46%, based on the ITT-population) showed an objective response, with two patients achieving a complete remission (CR).

Patients treated with MOR202 plus DEX had a median of five prior treatment regimens before study entry. Median PFS of this cohort was 4.7 months, with a median follow-up of 22.1 months. 5 out of 18 patients (28%, based on the ITT population) had an objective response.

Details of the MOR202 presentation at ASCO (Free ASCO Whitepaper) 2017

Abstract #8024, poster board #350

MOR202 with low-dose dexamethasone (DEX) and in combination with pomalidomide/DEX and lenalidomide/DEX in relapsed or refractory multiple myeloma (RRMM): Interim analysis of a phase 1/2a dose-escalation study

The poster will be presented during the "Hematologic Malignancies – Plasma Cell Dyscrasia" session on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall).

MorphoSys will hold an Investor & Analyst Event at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting on June 5, 2017, at 6:30pm CDT (June 6, 2017: 1:30am CEST). Clinical data for MorphoSys’s investigational agents MOR208 and MOR202 will be presented by clinical investigators and company representatives.

A replay and the presentation will be made available at View Source

Live-Webcast: https://services.choruscall.com/dataconf/productusers/morph/mediaframe/19794/indexl.html

About MOR202 and the ongoing phase 1/2a study in multiple myeloma
The investigational drug MOR202 is a fully human HuCAL antibody directed against CD38, a highly expressed and validated target in multiple myeloma. Data are from an ongoing clinical phase 1/2a, open-label, multi-center, dose-escalation study conducted in several sites in Germany and Austria. The study is evaluating the safety and preliminary efficacy of MOR202 with low dose dexamethasone and in combination with the immunomodulatory drugs (IMiDs) pomalidomide (POM) and lenalidomide (LEN) plus DEX in patients with relapsed/refractory multiple myeloma. The primary endpoints of the trial are the safety, tolerability and recommended dose of MOR202 with DEX and in combination with the IMiDs. Secondary outcome measures are pharmacokinetics and preliminary efficacy based on overall response rate, duration of response, time-to-progression, and progression-free survival.

MediciNova Announces Positive Results from a Glioblastoma Animal Model Study Presented at the 2017 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois

On June 5, 2017 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported that Associate Professor Kerrie McDonald, Head of the Cure Brain Cancer Foundation Biomarkers and Translational Research Group at the Lowy Cancer Research Centre, University of New South Wales, today presented positive results from an animal model study that examined the potential clinical efficacy of MN-166 (ibudilast) for the treatment of glioblastoma at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 5th , 2017 in Chicago, Illinois (Press release, MediciNova, JUN 5, 2017, View Source [SID1234519412]).

Major highlights of the presentation titled "Treating glioblastoma with a cytokine inhibitor, ibudilast in combination with temozolomide extends survival in a patient derived xenograft model," are summarized as follows:

Tumor samples from glioblastoma (GBM) patients, divided into two groups according to overall survival (i.e., "poor survivors" were defined by survival of less than 12 months and "good survivors" were defined by survival of more than 12 months) were examined for protein overexpression.
Proteomics analysis in frozen GBM tissues identified Macrophage Migration Inhibitory Factor (MIF) overexpression in the cells from "poor survivors;"
Among 168 GBM patient-derived tumor tissue samples, MIF and its receptor CD-74 were significantly over-expressed in 57% of patients and were found to be associated with poor survival.
A mouse model of GBM was developed by using patient-derived GBM cells and treated with temozolomide (TMZ) (10mg/kg) alone and combination with ibudilast (5mg/kg or 20mg/kg). Findings from this mouse model included the following:

Median survival for the group that received TMZ treatment-only increased by 5 days (105.5 days p=0.054) compared to the control group;
Median survival for the group that received combination treatment of ibudilast (5mg/kg or 20mg/kg) with TMZ increased by 13.5 days and 11 days, respectively (114 days and 111.5 days, respectively, (p=0.005)), compared to the control group.
Median survival for the control group (i.e., no treatment) was 100.5 days.
Significant synergism between ibudilast and TMZ was observed.
MediciNova is currently preparing to initiate a Phase 2 clinical trial for the treatment of recurrent Grade IV glioblastoma with University of Sydney Royal North Shore Hospital.

About Glioblastoma

Malignant primary brain tumors represent the most frequent cause of cancer death in children and young adults and account for more deaths than melanoma. According to the American Association of Neurological Surgeons, glioblastoma (GBM) is an aggressive, extremely lethal form of brain malignancy that develops from glial cells (astrocytes and oligodendrocytes) and rapidly grows and commonly spreads into nearby brain tissue. GBM is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that GBM represents 15% of all brain tumors and 55% of all gliomas and has the highest number of cases of all malignant tumors, with an estimated 12,390 new cases predicted for 2017. Despite decades of advancements in neuroimaging, neurosurgery, chemotherapy, and radiation therapy, only modest improvements have been achieved and the prognosis has not improved for individuals diagnosed with GBM. Median survival is 14.6 months and only approximately 5% of GBM patients survive longer than 36 months.

About MN-166 (ibudilast)

MN-166 (ibudilast) has been marketed in Japan and Korea since 1989 to treat post-stroke complications and bronchial asthma. MediciNova is developing MN-166 for progressive MS and other neurological conditions such as ALS and drug use disorders. MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule phosphodiesterase (PDE) -4 and -10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glia cells, which play a major role in certain neurological conditions. Ibudilast’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical study results and provide the rationale for its therapeutic utility in neurodegenerative diseases (e.g., progressive MS and amyotrophic lateral sclerosis [ALS], also known as Lou Gehrig’s disease), substance abuse/addiction and chronic neuropathic pain.

Peregrine Pharmaceuticals Presents Preliminary Correlative Analysis of PD-L1 Expression from SUNRISE Trial at ASCO 2017

On June 5, 2017 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by advancing its proprietary R&D pipeline and manufacturing high quality products for biotechnology and pharmaceutical companies, reported the presentation of promising new data from its Phase III SUNRISE trial of bavituximab in patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, Peregrine Pharmaceuticals, JUN 5, 2017, View Source [SID1234519407]). Presented results demonstrated that patients in the study’s bavituximab treatment arm who had low baseline PD-L1 expression levels had a statistically significant improvement in median overall survival (mOS) as compared to patients in the same treatment arm who had higher baseline levels of PD-L1. Data were presented by Peregrine scientists at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), being held June 2 – 6, 2017 in Chicago.

Data presented demonstrated that patients in the study’s docetaxel plus bavituximab (D+B) treatment arm with a pre-treatment PD-L1 expression level on tumor cells of < 1% (TC0) had a mOS of 12.1 months compared to a mOS of 6.1 months for patients with PD-L1 expression ≥1% (TC1/2/3) (HR = 0.42 p=0.007). There was no difference in mOS based on PD-L1 expression levels observed in the study’s docetaxel plus placebo (D+P) control arm (10.7 months for TC0 vs. 11.1 months for TC1/2/3; HR = 0.87; p=0.609).

"We believe that these latest observations from the SUNRISE trial further support the hypothesis that bavituximab, through its immune modulating mechanism, may have more effect on tumors without pre-existent immunity. These ‘cold’ tumors suppress normal anti-tumor immune response and are categorized by very low to no PD-L1 expression on tumor cells," said Joseph Shan, vice president of clinical and regulatory affairs at Peregrine. "These latest findings, along with other recently announced clinical and preclinical data from our PS-targeting program, inform our clinical development strategy going forward and provide additional rationale for combining bavituximab with checkpoint inhibitors."

As part of the SUNRISE clinical study protocol, researchers requested but did not require that patients provide a tumor tissue sample at the time of diagnosis. In total, tissue samples were collected from 129 of the trial’s 597 patients and were assessed retrospectively for baseline PD-L1 expression levels on tumor cells. Of the 129 tissue samples collected, 122 were evaluable for PD-L1 expression on tumor cells (54 in D+B arm and 68 in D+P control arm). Of the evaluable samples in the D+B arm, 69% demonstrated PD-L1 expression levels < 1%, as compared to 59% in the D+P arm.

Bavituximab is an investigational immune-modulatory monoclonal antibody that targets phosphatidylserine (PS). PS inhibits the ability of immune cells to recognize and fight tumors. Bavituximab is believed to reverse PS-mediated immunosuppression by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. PS-targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses.

Peregrine’s clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes grants awarded by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations. These trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with Memorial Sloan Kettering Cancer Center (MSK) with the goal of evaluating combinations of PS targeting antibodies with checkpoint inhibitors and other immune stimulatory agents. Peregrine’s intent behind this strategy is to focus its research and development spending to further validate bavituximab’s combination potential as the company seeks to advance the program though a pharmaceutical or biotechnology partner.

Onconova Therapeutics Announces Positive Phase 2 Data in Rigosertib Treated Patients with Second-line Myelodysplastic Syndromes at the American Society of Clinical Oncology Annual Meeting

On June 5, 2017 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported the results of a Phase 2 study with rigosertib as a treatment for higher risk (HR-MDS) after failure of hypomethylating agents (HMAs) (Press release, Onconova, JUN 5, 2017, View Source [SID1234519406]). The study sought to evaluate bone marrow blast (BMBL) response to rigosertib as a surrogate for overall survival (OS) in this patient population. The results showed treatment with rigosertib resulted in a reduction in BMBL count, including complete bone marrow responses, confirming findings in earlier studies. Thus, BMBL response to rigosertib is a potential surrogate marker for improvement in overall survival in this patient population.

"In this new study for HR-MDS patients after failure of HMA therapy, we are excited to confirm a correlation between blast reduction and prolongation of survival in rigosertib treated patients. These results build upon our previous findings in the ONTIME trial showing improvement in overall survival in patients with the highest risk prognostic categories after failure of HMA treatment (ASH 2014 presentation),"said Ramesh Kumar, Ph.D., President and CEO of Onconova.

Rigosertib is currently being tested in a randomized, global, Phase 3 INSPIRE trial for this patient population.

Study Name: Relationship of Bone Marrow Blast response to Overall Survival in a Multicenter Study of Rigosertib in Patients with Myelodysplastic Syndromes with Excess Blasts Progressing on or After Treatment with a Hypomethylating Agent

Summary of Data from the 04-24 Trial

Patient Demographics:

64 patients treated, with a median age of 73, median prior HMA duration of 10.8 months.
Eligible patients had 5%-30% BMBL confirmed within six weeks pre-study and disease. progression as per International Working Group (IWG) 2006 criteria, Cheson et al., Blood 2006) on or after HMAs within two years.
Safety/Tolerability:

Intravenous rigosertib has been well tolerated to date.
More than 1,100 patients have been treated with rigosertib.
Adverse events in study 04-24 were similar to those observed in the preceding Phase 3 ONTIME Study
Objectives:

Primary Efficacy: Evaluate the relationship between BMBL response and OS in MDS patients with excess blasts (5-30%) progressing on or after treatment with azacitidine or decitabine who are administered 72-hr continuous intravenous (IV) infusions of 1800 mg/24 hour rigosertib every 2 weeks for 8 cycles and every 4 weeks thereafter. BMBL response is defined according to the International Working Group (IWG) 2006 criteria; or stable BM response (no progression),
Secondary Efficacy: Evaluate the following parameters: Overall response (CR, partial response/remission [PR], BMCR, and stable disease [SD]) according to 2006 IWG criteria; Population pharmacokinetics.
Safety: safety and tolerability of rigosertib administered as 72-hour continuous IV (5%-30% BMBL) progressing on or after treatment with azacitidine or decitabine.
Trial Design:

Phase 2 open-label, multi-center multi-national study (approximately 30-40 Centers in the US and Europe) of the efficacy and safety of Rigosertib administered as 72-hour continuous intravenous infusions in patients with myelodysplastic syndromes with excess blasts progressing on or after treatment with azacitidine or decitabine.
Treatment will continue until IWG 2006 progression criteria are met (ie, 50% increase of BMBL or worsening of cytopenias) or until death from any cause, whichever comes first.
Following these results, all patients will be followed until death and/or progression, even if they have discontinued treatment for any reason. View the complete study poster HERE.

NewLink Genetics’ Indoximod + PROVENGE® Results in Statistically Significant Improvement in Radiographic Progression-Free Survival (rPFS) for Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC) in Phase 2 Trial

On June 5, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported the presentation of results from a randomized Phase 2 investigator initiated study with indoximod in combination with the therapeutic cancer vaccine, PROVENGE (sipuleucel-T), for patients with metastatic castration resistant prostate cancer (Press release, NewLink Genetics, JUN 5, 2017, View Source [SID1234519404]). The abstract, titled A phase 2 randomized, double-blind study of sipuleucel-T followed by IDO pathway inhibitor, indoximod, or placebo in the treatment of patients with metastatic castration resistant prostate cancer (mCRPC), is being presented in a poster session by Gautam G. Jha, M.D., Adjunct Assistant Professor, Division of Hematology and Oncology, University of Minnesota, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, IL this morning from 8:00-11:30 a.m. CT.

In the study, forty-six patients were randomized into two arms to receive either twice daily oral indoximod (n=22) or placebo (n=24) for 6 months beginning the day after the third and final PROVENGE infusion. The indoximod treatment arm for the study showed a statistically significant improvement in radiographic progression-free survival (rPFS) when compared to placebo and was well tolerated.

Key findings presented from the study include:

Statistically significant improvement in median rPFS was 10.3 months in the treatment arm compared to 4.1 months in the placebo arm (p = 0.011)
Median Overall Survival (OS) has not yet been reached
Patients tolerated therapy with indoximod with no significant differences in adverse events between the two arms
There was no statistical difference in the primary endpoint of ELISPOT assay immune response to PA2024, the PROVENGE-related fusion protein, in the 35 of 46 patients who had clinical samples available for testing
"Given that PROVENGE alone has not shown any PFS benefit in multiple prior studies, this randomized, placebo controlled data, although limited in number of patients, is quite encouraging and has the potential to offer some measurable clinical benefits for patients," said Dr. Jha, principal investigator of this study.

An infographic accompanying this release is available at View Source

Data reported at ASCO (Free ASCO Whitepaper) 2017 indicate that treatment with NewLink Genetics’ proprietary IDO pathway inhibitor, indoximod, post PROVENGE therapy leads to significant improvement in rPFS when compared to placebo and is well tolerated.

"These results are additional evidence that indoximod has the potential to improve outcomes for patients in combination with therapies beyond the established checkpoint inhibitors," said Charles J. Link, Jr. M.D., Chairman and CEO of NewLink Genetics.