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MOLOGEN’s presentations well received at ESMO 2017

On September 13, 2017 The biopharmaceutical company MOLOGEN AG (ISIN DE0006637200; Frankfurt Stock Exchange Prime Standard: MGN)reported two sets of data on its lead compound, the immunotherapeutic agent lefitolimod, at the European Society for Medical Oncology (ESMO 2017) in Madrid (8 – 12 September 2017) (Press release, Mologen, SEP 13, 2017, View Source [SID1234520530]). The coordinating investigator Prof. Dr. Michael Thomas, MD, Head of the Department Oncology/Internal Medicine at the Thorax Clinic at University of Heidelberg, Germany, gave an oral presentation on the top-line data from the exploratory, signal-seeking phase II IMPULSE trial in extensive-disease small-cell lung cancer in a Proffered Paper Session with the session’s co-chair, Prof. Sanjay Popat, The Royal Marsden Hospital, London, acting as invited discussant. Furthermore, data on lefitolimod as modulator of the tumor microenvironment (TME) alone and in combination with immune checkpoint inhibitors in pre-clinical tumor models were presented in the Translational Research Poster Session.

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Promising overall survival signal in pre-defined subgroups of IMPULSE

The exploratory randomized IMPULSE study which evaluates the efficacy and safety of lefitolimod in patients with extensive-disease small-cell lung cancer (SCLC) showed noteworthy results in the primary analysis regarding overall survival (OS) in two clinically relevant subgroups of patients in comparison to the control group (standard therapy). A signal for an OS benefit was seen in patients with reported Chronic Obstructive Pulmonary Disease (COPD), a frequent underlying disease.

Notably, a strong OS signal was observed in patients with a low count of activated B cells, an important immune parameter, at baseline. This contributes to the hypothesis that activated B cells may serve as a valid biomarker in the further development of lefitolimod in this relevant subgroup of extensive-disease SCLC patients. The invited discussant Prof. Popat interpreted IMPULSE as a signal-generating study with an interesting hypothesis which merits further evaluation.

"To our knowledge IMPULSE is the first randomized controlled clinical study of a maintenance therapy following first-line chemotherapy in extensive-disease SCLC showing a promising overall survival signal in a pre-specified subgroup. The study provides important guidance for defining patient populations most likely to benefit from treatment with lefitolimod in further clinical trials," said Dr. Matthias Baumann, Chief Medical Officer of MOLOGEN AG. "I am also delighted that the European Thoracic Oncology Platform (ETOP) asked Prof. Thomas for permission to publish his presentation on their website which, in our view, underlines the interest of the scientific community in our approach."

Lefitolimod-induced modulation of the tumor microenvironment supports its potential as ideal partner for immune-oncology combination therapies

The lefitolimod-induced pathway provides the rationale for combining lefitolimod with checkpoint inhibitors (CPI). First combination data of lefitolimod with checkpoint inhibitors in mouse tumor models have been presented at the Annual 2017 Gastrointestinal Cancers Symposium in San Francisco, USA (January 19-21, 2017). The data showed that lefitolimod can significantly improve the anti-tumor effect of checkpoint inhibitors, particularly anti-PD-1 and anti-PD-L1 antibodies, and thus prolong survival in murine colon carcinoma and lymphoma tumor models.

Response rates to checkpoint inhibitor immunotherapy vary between different tumor entities and depend on the nature of the tumor microenvironment (TME). Hot tumors with a T cell-infiltrated TME show better responses. Therefore, modulation of the TME is a crucial requirement for the response to immunotherapeutic approaches.

MOLOGEN’s current data showed that monotherapy with lefitolimod resulted in a modulation of the TME in a colon carcinoma tumor model after intra-tumoral injection. An increased infiltration of T cells, especially cytotoxic T cells, into the tumor was shown, which was associated with reduced tumor growth. This beneficial modulation of the TME by lefitolimod supports its potential in cancer immunotherapy. Hence, lefitolimod may be an ideal partner for immune-oncology combination approaches, i.e. with checkpoint inhibitors.

Background to the IMPULSE small-cell lung cancer (SCLC) study

The trial titled "Randomized Clinical Study of Maintenance Therapy with Immunomodulator MGN1703 in patients with Extensive Disease Small Cell Lung Cancer after Platinum-Based First-Line Therapy" (IMPULSE study) is an explorative study and has overall survival as the primary endpoint. It compares lefitolimod (MGN1703) versus standard therapy (chemotherapy). The study included 102 patients suffering from extensive-disease small-cell lung cancer and showing at least partial response to four cycles of first-line chemotherapy. They were randomized at a ratio of 3:2 to switch-maintenance therapy with lefitolimod (60mg injected subcutaneously twice weekly) or standard therapy until disease progression.

There will be a final read-out probably in the first quarter of 2018, approximately 24 months following the recruitment of the last patient.

Further information can be found on MOLOGEN’s website:

Phase I study of 4SC’s resminostat indicates efficacy in biliary tract cancer

On September 13, 2017 4SC AG (4SC, FSE Prime Standard: VSC) reported that the Company’s development partner Yakult Honsha together with the investigators presented promising results of a multi-center, open-label Phase I study of 4SC’s resminostat in combination with S-1 chemotherapy in 27 Japanese patients with pre-treated biliary tract or pancreatic cancer at the ESMO (Free ESMO Whitepaper) 2017 Congress. The study was conducted by Yakult Honsha in Japan (Press release, 4SC, SEP 13, 2017, View Source [SID1234520529]). S-1 is a chemotherapy combination drug which is approved for the treatment of several solid tumor types including biliary tract or pancreatic cancer in Asia.

The primary objective of the study was to investigate the dose-limiting toxicities of resminostat monotherapy as well as the combination of resminostat and S-1 chemotherapy to determine the recommended regimen that should be used in a subsequent Phase II study. The secondary objectives included safety and efficacy parameters.

Chigusa Morizane, M.D., from the Department of Hepatobiliary and Pancreatic Oncology at the National Cancer Center Hospital in Tokyo, Japan, summarized the results: "As planned, from three different dose and schedule cohorts, we identified a well-tolerated regimen of resminostat/S-1 combination therapy. We observed tumor shrinkage or disease stabilization in all patients with biliary tract cancer receiving second-line study treatment according to the recommended regimen. Advanced biliary tract cancers are highly lethal, but in patients receiving the combination of resminostat and S-1 chemotherapy we saw a remarkable median overall survival of 10.2 months with no disease progression for 5.5 months (in median). Overall, 3 patients continued study treatment for over 180 days and the treatment of 1 patient is still ongoing."

Frank Hermann, M.D., Chief Development Officer of 4SC, commented: "We are very pleased with these promising data. Yakult Honsha confirmed further investigation of the efficacy of resminostat/S-1 combination treatment in Japanese second line biliary tract cancer patients in a subsequent Phase II study to commence in the near future. In parallel, 4SC is continuing to evaluate resminostat for maintenance treatment in patients with advanced-stage cutaneous T-cell lymphoma in our pivotal RESMAIN study in Europe."

INSPYR THERAPEUTICS AND LEWIS AND CLARK PHARMACEUTICALS COMPLETE MERGER

On September 13, 2017 Inspyr Therapeutics (OTCQB:NSPXD), a clinical-stage biotechnology company, and Lewis and Clark Pharmaceuticals reported the successful completion of a merger to create an integrated biotechnology company (Press release, Inspyr Therapeutics, SEP 13, 2017, View Source [SID1234520528]). The newly combined company creates a second proprietary technology platform, broad capability laboratory facilities, pipeline of therapeutics, and drug development expertise to create value across the business.

"This merger has significantly broadened the opportunities we can pursue, spanning from the discovery of new molecules through clinical development," said Peter Grebow Ph.D., Chairman of Inspyr. "We believe the proprietary technology platform acquired from Lewis & Clark will generate a series of partnerships or collaborations in the near future. The initial proprietary molecules generated on this platform are expected to have novel development applications in immuno-oncology and inflammation."

Key strategic benefits of the merger:

Novel proprietary technology platform. The Company now has an industry-leading proprietary technology platform based on adenosine chemistry and biology. From this platform, multiple adenosine receptor modulator-based compounds have been developed and are advancing into preclinical studies to support planned Investigational New Drug (IND) applications. Inspyr is pursuing potential license opportunities to leverage this platform.
Broad pipeline of novel therapies for oncology and inflammation. The Company pipeline of novel proprietary therapies currently includes Mipsagargin, dual A2A/A2B antagonists, A2A antagonists, A2B antagonists, and A2A agonists.
State-of-the-art laboratory facilities. The Company has a fully-equipped, state-of-the-art organic and analytical chemistry laboratories located in Charlottesville, Virginia. We believe the value of these assets is significantly greater than the combined market caps at closing.
Experienced leadership. Inspyr’s team has significant clinical development, translational medicine, and business operations experience in the biopharmaceutical industry. Through this merger, the Company’s expertise has expanded to include preclinical development, toxicology, regulatory filings, adenosine receptor pharmacology, physiology, and molecular biology.
Collaboration Agreements. With broad capabilities, laboratory facilities, and extensive drug discovery and development expertise, Inspyr anticipates the first of a series of licensing/collaboration agreements in Q4 2017.
Potential Stock Exchange Listing. Inspyr expects to complete an uplisting to NASDAQ as soon as practical upon meeting the shareholder equity qualification standard.
Under the merger agreement, Inspyr purchased Lewis and Clark in an all-stock transaction. Pursuant to the terms of the transaction, Lewis and Clark Pharmaceuticals is now a wholly-owned subsidiary of Inspyr and Lewis and Clark stockholders own approximately 50% of Inspyr’s common shares, on an as converted basis. In addition, Bo Jesper Hansen, M.D., Ph.D. is retiring from Inspyr’s Board of Directors and Lewis and Clark Director John Montgomery has been appointed to the Inspyr Board of Directors.

Reata Pharmaceuticals, Inc. Receives Orphan Drug Designation for Omaveloxolone for the Treatment of Malignant Melanoma

On September 13, 2017 Reata Pharmaceuticals, Inc. (Nasdaq:RETA) (“Reata” or “the Company”), a clinical-stage biopharmaceutical company, reported that the United States Food and Drug Administration (“FDA”) has granted orphan designation to omaveloxolone for the treatment of Stage IIb through IV malignant melanoma (Press release, Reata Pharmaceuticals, SEP 13, 2017, View Source [SID1234520527]).

Reata is currently executing a Phase 1b/2 trial evaluating the safety and efficacy of omaveloxolone in combination with nivolumab or ipilimumab in patients with unresectable or metastatic melanoma who have failed anti-PD-(L)1 therapies. The purpose of the Phase 1b portion of the trial is to identify a recommended Phase 2 dose by collecting blood, tumor biopsy, and radiographic data to determine if omaveloxolone can unmask tumors, restore immune response, and demonstrate anti-cancer activity.

Orphan status is granted to treatments for diseases that affect fewer than 200,000 people in the United States and provides specific incentives for therapies intended for the treatment, diagnosis, or prevention of rare diseases. The orphan designation will provide Reata with development incentives, including tax credits for clinical testing, exemption from a prescription drug user fee, and seven years of market exclusivity.

OncoMed Doses First Patient with GITRL-Fc in Phase 1a Clinical Trial

On September 13, 2017 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported that the first patient has been dosed in the company’s Phase 1a clinical trial of GITRL-Fc (OMP-336B11) (Press release, OncoMed, SEP 13, 2017, View Source [SID1234520507]). GITRL-Fc is an investigational immuno-oncology therapeutic candidate designed to leverage the natural trimeric ligand to modulate the tumor microenvironment by inhibiting T-regulatory cells and activating T-effector cells.

"The 1st generation immuno-oncology agents, which work by blocking the activation of inhibitory receptors on T cells, have produced impressive results in a number of tumor types," said Kyriakos Papadopoulos, M.D. at South Texas Accelerated Research Therapeutics (START) in San Antonio, TX and a lead investigator for the Phase 1a study. "GITRL-Fc is designed to directly agonize the GITR T cell activation receptor, resulting in increased T-effector cells and a reduction in the number of T-regulatory cells. OncoMed’s agent has demonstrated anti-tumor activity in pre-clinical studies, and as a result, we are excited to initiate this Phase 1a clinical trial of GITRL-Fc."

The Phase 1a open-label clinical trial is designed to assess the safety and tolerability of escalating doses of GITRL-Fc in patients with advanced or metastatic solid tumors. Secondary objectives for the trial include characterization of the pharmacokinetics, immunogenicity and anti-tumor efficacy. Pharmacodynamic and potential predictive biomarkers focused on changes in immune system activation will also be explored. GITRL-Fc will be administered as a single agent every two weeks at escalating dose levels. Once a maximum-tolerated dose has been achieved, an expansion cohort will enroll patients with certain tumor types. The trial will be conducted at five centers in the U.S. and is expected to enroll approximately 30 patients.

"GITRL-Fc is a fusion protein consisting of the fully human natural trimer GITR ligand linked to an Fc. Pre-clinical experiments have suggested that this agent may be a more potent agonist of the GITR trimer receptor than bivalent agonist antibodies," said Robert Stagg, Pharm.D., OncoMed’s Senior Vice President of Clinical Research and Development. "As a result, we are very pleased to have initiated this Phase 1a trial which will help to define the maximum tolerated dose, safety and preliminary efficacy of this immuno-oncology agent."

About GITRL-Fc
GITR (glucocorticoid-induced TNFR-related protein) is a costimulatory molecule that has been shown to be involved in inhibiting the suppressive activity of T-regulatory cells and extending the survival of T-effector cells. Leveraging OncoMed’s proprietary linkerless gene trimer technology, OncoMed has developed a differentiated approach to targeting the GITR/GITRL axis by creating a fusion protein with an Fc-linked fully human trimer ligand that may be more amenable to the natural receptor’s trimeric structure. GITRL-Fc is designed to modulate the tumor microenvironment by inhibiting T-regulatory function and activating T-effector cells. In preclinical studies, a surrogate GITRL-Fc showed superior GITR signaling activation, T-cell proliferation and cytokine production in human T-cell models as compared to two anti-GITR mAbs in competitive development and demonstrated potent in vivo anti-tumor activity. GITRL-Fc is currently being studied in a Phase 1a study in patients with solid tumors. OncoMed is independently developing GITRL-Fc.