On January 8, 2019 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 the first glioblastoma patient has enrolled in the clinical trial of MN-166 (ibudilast) in combination with temozolomide (TMZ, Temodar‑) for the treatment of recurrent glioblastoma (GBM) (Press release, MediciNova, JAN 8, 2019, View Source;p=RssLanding&cat=news&id=2382746 [SID1234532592]). The principal investigators are Patrick Y. Wen, M.D., Professor of Neurology, Harvard Medical School and Director, Neuro-Oncology Division at the Dana-Farber Cancer Institute (DFCI) in Boston, and Kerrie McDonald, Ph.D., Associate Professor and Head of Biomarkers and Translational Research at the Lowy Cancer Research Centre, University of New South Wales, Australia.

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The scientific rationale for this clinical trial is based on positive results from preclinical studies conducted by Dr. McDonald and her team. MN-166 (Ibudilast) and temozolomide (TMZ) combination treatment significantly increased GBM cell apoptosis and cell cycle arrest in an in-vitro study. Combination treatment of MN-166 (ibudilast) with TMZ resulted in significantly extended survival times compared to TMZ monotherapy in a GBM animal model study with complete tumor regression observed in two out of 16 mice. This is the first clinical trial to evaluate the safety, tolerability and preliminary efficacy of MN-166 (ibudilast) in combination with temozolomide for the treatment of recurrent GBM.

Patrick Y. Wen, M.D., principal investigator, commented, "We are very excited to study ibudilast with TMZ combination treatment as we believe ibudilast’s mechanisms of action and good penetration of the blood-brain barrier could benefit patients with recurrent GBM."

Kerrie McDonald, Ph.D., Associate Professor, University of New South Wales, Australia, commented, "Earlier studies indicate that macrophage migration inhibitory factor (MIF) and phosphodiesterase (PDE)-4 may factor in proliferation of GBM tumors. MIF was found to be highly expressed within GBM cells, and especially around necrotic areas and in close proximity to blood vessels. Ibudilast in combination with TMZ resulted in significant blockage of MIF expression, increased apoptosis, and longer survival in vivo."

Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented, "We are very pleased that enrollment has commenced for this trial at Dana-Farber Cancer Institute, one of the most highly rated cancer treatment institutions in the U.S. We believe MN-166 offers a novel approach to treating GBM, a highly lethal form of cancer that develops from glial cells."

About the Clinical Trial

This Phase 1/2 clinical trial is divided into a dose-escalation phase (Part 1) followed by a fixed-dose phase (Part 2). A total of 15-18 adult subjects are planned to be enrolled in Part 1 and approximately 32 subjects are planned to be enrolled in Part 2. Part 1 will evaluate the safety and tolerability of MN-166 (ibudilast) when given in combination with TMZ, and determine the dose of MN-166 (ibudilast) to be used in Part 2 of the study. Part 2 will evaluate the efficacy of MN-166 (ibudilast) and temozolomide combination treatment in patients with recurrent GBM as measured by the proportion of patients who are progression-free at 6 months. Other outcome measures include the evaluation of overall survival, response rate, and median six-month progression-free survival.

About Glioblastoma

According to the American Association of Neurological Surgeons, GBM is a devastating brain cancer that typically results in death in the first 15 months after diagnosis. GBM 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 56% of all gliomas and has the highest number of cases of all malignant tumors, with an estimated 12,760 new cases predicted for 2018. 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 two-year survival is 30%. Approximately 5% of GBM patients survive longer than 36 months.

About MN-166 (ibudilast)
MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glial cells, which play a major role in certain neurological conditions. MN-166 (ibudilast)’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical studies, which provide the rationale for treatment of progressive multiple sclerosis (MS) and other neurological diseases such as amyotrophic lateral sclerosis (ALS), substance abuse/addiction and glioblastoma (GBM). MediciNova is developing MN-166 for progressive MS and other neurological conditions such as ALS, substance abuse/addiction, chemotherapy-induced neuropathy, and glioblastoma. MediciNova has a portfolio of patents which cover the use of MN-166 (ibudilast) to treat various diseases including progressive MS, ALS, and drug addiction.

On January 8, 2019 CSPC Pharmaceutical Group Ltd. agreed to acquire Hong Kong-based Yong Shun Technology Development for about 252.9 million yuan (Press release, CSPC Pharmaceutical, JAN 8, 2019, View Source [SID1234605494]). CSPC unit Dragon Merit Holdings Ltd. will acquire all issued shares of Yong Shun, subject to certain conditions. CSPC said the deal is in line with its strategy to seek acquisition targets with strong research and development capabilities in the biopharmaceutical drug market. As of Jan. 7, US$1 was equivalent to 6.85 yuan.

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On January 8, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that it has achieved a USD 75 million sales volume milestone in its DARZALEX (daratumumab) collaboration with Janssen Biotech, Inc (Press release, Genmab, JAN 8, 2019, View Source [SID1234532577]). The milestone was triggered by confirmation by Janssen that sales of DARZALEX reached USD 2 billion in the calendar year of 2018. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize DARZALEX.

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"We are very pleased that as the launch continues, DARZALEX has become available to so many more multiple myeloma patients in need, which is reflected in the achievement of this sales milestone. With the potential for further indications to be approved in the future, we look forward to even greater growth in the coming years," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The milestone payment was included in the financial guidance issued by Genmab originally on February 21, 2018 and then reiterated in subsequent quarterly financial reports, most recently on November 14, 2018, and as such there is no change to the company’s financial guidance for 2018.

On January 8, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing therapies designed to activate a patient’s immune system against cancer, reported that the Company’s principal investigator for its Phase 2 Lung Cancer Trial, Daniel Morgensztern, MD, Associate Professor of Medicine and Director of Thoracic Oncology, Washington University School of Medicine, has been selected to deliver an oral presentation of his abstract summarizing new interim data from the Company’s Phase 2 trial of HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo), in patients with advanced non-small cell lung cancer (NSCLC) at the 2019 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium (Press release, Heat Biologics, JAN 8, 2019, View Source [SID1234532579]).

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The 2019 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium will be held from February 28-March 2, 2019 at the San Francisco Marriott Marquis. The details for the oral presentation at the 2019 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium are as follows:

Title: Viagenpumatucel-L (HS-110) plus nivolumab in patients with advanced non-small cell lung cancer (NSCLC)

Date and time: February 28, 2019 at 1:00 PM to 2:15 PM PST

Session title: Oral Abstract Session A: Lung Cancer

Abstract number: 101

On January 8, 2019 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported a corporate update on the Company’s clinical development of galinpepimut-S (GPS) and nelipepimut-S (NPS), which are both in late-stage development (Press release, Sellas Life Sciences, JAN 8, 2019, View Source [SID1234532580]).

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"In 2018, SELLAS achieved significant progress towards our corporate and clinical goals, as we advanced our immunotherapy pipeline and completed our first year as a public company," said Dr. Angelos M. Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "As we look to 2019, we are excited to initiate our pivotal Phase 3 program for GPS in acute myeloid leukemia (AML), and are in active discussions with the U.S. Food and Drug Administration (FDA) regarding the registration-enabling Phase 3 trial and potential consideration for accelerated approval and breakthrough designation for NPS to treat triple negative breast cancer. We also are exploring the potential of GPS in combination with pembrolizumab in additional tumor types in the context of a Phase 1/2 basket clinical study and look forward to continued progress across our broad pipeline in the year ahead."

Galinpepimut-S (GPS)

In November 2018, SELLAS aligned with the FDA on the clinical trial design and biostatistical plan for a Phase 3 registrational study for GPS in acute myeloid leukemia (AML). The planned Phase 3 registrational study will be a 1:1 randomized, open-label study comparing GPS in the maintenance setting to investigators’ choice of best available treatment (BAT) in adult AML patients who have achieved hematologic complete remission, with or without thrombocytopenia (CR2/CR2p), after second-line antileukemic therapy and who are deemed ineligible for or unable to undergo allogeneic stem-cell transplantation. This study will serve as the basis for a Biologics License Application (BLA) submission, subject to positive results, and SELLAS expects to start the Phase 3 trial in the second quarter of 2019.

The Phase 3 study is expected to enroll approximately 116 patients at approximately 50 clinical sites in the United States and Europe. The primary endpoint is overall survival (OS) and secondary endpoints include leukemia-free survival, antigen-specific T-cell immune response dynamics over time and rates of achievement of measurable residual disease (MRD) negativity. The study will have a planned interim safety and futility analysis after 80 events, expected to occur in the third quarter of 2020. GPS was previously granted Fast Track and Orphan Drug designations by the FDA for the treatment of AML.

In December 2018, SELLAS initiated enrollment of the Phase 1/2 open-label, non-comparative, multicenter, multi-arm study of GPS in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with selected WT1-positive advanced cancers, including both hematologic malignancies and solid tumors. This study, which is being conducted under a Clinical Trial Collaboration and Supply Agreement (CTSA) with Merck (known as MSD outside the United States and Canada), will assess the efficacy and safety of the combination, with exploratory long-term follow-up for overall survival and safety. The study will enroll approximately 90 patients at up to 20 centers in the United States. The initial tumor types to be treated will be acute myelogenous leukemia (AML) (patients unable to attain deeper morphological response than partial on hypomethylating agents and who are not eligible for allogeneic hematopoietic stem cell transplant) and ovarian cancer (second or third line), to be followed by triple negative breast cancer (second line), small cell lung cancer (second line), and colorectal cancer (third or fourth line).

Nelipepimut-S (NPS)

Based on promising Phase 2b data presented in 2018, SELLAS is currently in continuing active discussions with the FDA regarding the optimal development path for NPS in triple negative breast cancer (TNBC).

In the Phase 2b study of trastuzumab (Herceptin) +/- nelipepimut-S (NPS) in HER2 low-expressing breast cancer patient cohorts, trastuzumab + NPS demonstrated clinically and statistically significant efficacy in the TNBC cohort, with a p-value of 0.013 and a 75.2% reduction in risk of relapse or death. In October 2018, the Data Safety Monitoring Board (DSMB) unanimously concluded that the final analysis of the Phase 2b study data with a median follow-up of 26 months confirmed that TNBC patients should be the key target population for the development of trastuzumab + NPS in the adjuvant setting in early-stage HER2 1+/2+ breast cancer patients.

A preplanned secondary efficacy analysis across human leukocyte antigen (HLA) allele subgroups from the Phase 2b study confirmed the therapeutic potential of NPS in patients with early-stage TNBC in the adjuvant setting across HLA types A-02, -03, -24 and -26, which cover approximately 80-85% of the North American/European populations and 86-90% of Asian/Pacific basin populations.

Additional positive data from the Phase 2b study showed a clinically meaningful and statistically significant decrease in the number of clinically detectable relapses in the TNBC cohort with the combination of trastuzumab + NPS (7.5%) vs. trastuzumab alone (27.3%) (p=0.004). In addition, four pre-defined subgroups of TNBC patients in the trastuzumab + NPS arm demonstrated an average decrease of 84.2% in relative risk of relapse or death at 24 months (p=0.004-0.014).

In a Type C meeting with the FDA, SELLAS discussed several key points of the clinical and regulatory strategy for NPS in combination with trastuzumab for TNBC, including potential for accelerated approval; a registration-enabling Phase 3 trial design and biostatistical plan; and the potential for breakthrough designation. SELLAS expects a further meeting with the FDA in early 2019 regarding the potential for breakthrough designation as well as an additional meeting in the first quarter of 2019 to reach agreement for a final development program for NPS in TNBC.

An abstract summarizing the comprehensive set of results from the final analysis of the NPS + trastuzumab Phase 2b clinical study has been accepted for an oral presentation at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium in San Francisco, CA, on March 2, 2019 at 10:15 AM.

NPS was previously granted Fast Track designation by the FDA for the adjuvant treatment of patients with early stage breast cancer with low to intermediate HER2 expression following standard of care upfront therapy (surgery plus chemotherapy +/- radiotherapy).

Expected 2019 Clinical Milestones

Regulatory and development program with FDA for NPS in TNBC patients finalized in Q1 2019.
Phase 3 registration-enabling study of GPS in AML patients initiated in Q2 2019, with a planned interim analysis expected in Q3 2020.
Interim analysis of Phase 1/2 basket study of GPS with pembrolizumab in multiple tumor types in Q4 2019.
Herceptin and Keytruda are registered trademarks of Genentech, Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA., respectively, and are not trademarks of SELLAS. The manufacturers of these brands are not affiliated with and do not endorse SELLAS or its products.