On April 24, 2017 The biopharmaceutical company MOLOGEN AG (ISIN DE0006637200; Frankfurt Stock Exchange Prime Standard: MGN) reported the key results of the exploratory phase II IMPULSE study (Press release, Mologen, APR 24, 2017, View Source [SID1234518676]). The randomized study evaluated the efficacy and safety of lefitolimod in patients with extensive-disease small-cell lung cancer (SCLC). IMPULSE shows positive results regarding overall survival (OS) in two subgroups of patients in comparison to the control group (standard therapy). Additional, potentially promising subgroups will be identified. The results of this SCLC study provide significant guidance for defining patient populations that, even beyond this study, are most likely to benefit from the immune surveillance reactivator lefitolimod, even though in this highly challenging indication the primary endpoint OS was not met in the overall study population.

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"Lung cancer, and especially small-cell lung cancer, is an indication for which the benefit of current standard treatment is very limited. We are therefore very pleased to see initial evidence of clinical efficacy for lefitolimod in small-cell lung cancer, an indication known for its setbacks in other drug development programs," said Dr Mariola Soehngen, CEO of MOLOGEN AG. "The data of the IMPULSE study, especially from the two identified subgroups, show that lefitolimod has the potential to become an important treatment option – also for patients with a disease as difficult to treat as small-cell lung cancer. Notably, these positive study results will be an important asset in the ongoing partnering discussions."

The IMPULSE study shows positive results in two pre-defined and clinically relevant subgroups of patients. Notably, a strong overall survival (OS) benefit was shown in comparison to the control arm (local standard of care) in patients with a low count of activated B cells (hazard ratio 0.59, 95% confidence interval 0.29-1.21), an important immune parameter. Moreover, a benefit was seen in patients with reported Chronic Obstructive Pulmonary Disease (COPD), a frequent underlying disease (hazard ratio 0.54, 95% confidence interval 0.21-1.38).

The safety profile of lefitolimod is favorable. The most common adverse events in the IMPULSE population were cough, asthenia, headache, nausea, and back pain. Adverse events may also be due to underlying diseases and/or adjunctive therapy.

"We have seen promising efficacy signals in subgroups of patients in this very difficult-to-treat- indication. We are committed to further analyze the data and to continue the development of lefitolimod in small-cell lung cancer, where there are no better current treatment options than chemotherapy. Therefore, an important medical need exists for new and/or complementary combination treatment alternatives. Moreover, it would also be helpful to evaluate lefitolimod in patients with SCLC in combination with other immuno-oncological drugs," said Dr Ronald Carter, Acting CMO of MOLOGEN AG.

The present findings from IMPULSE provide additional key insights into the role of TLR9 agonists in the treatment of cancer, and confirm there is significant opportunity to improve outcomes for patients in this therapeutic area.

A more extensive evaluation of the IMPULSE data is currently ongoing. The full IMPULSE study results will be presented at international scientific conferences.

MOLOGEN’s ongoing development programs, especially the pivotal IMPALA study, are running independently from these study results, given these are different indications.

Three more clinical studies with lefitolimod

Further to the IMPULSE study, lefitolimod is currently being evaluated in the pivotal phase III IMPALA study for first-line maintenance treatment of metastatic colorectal cancer (mCRC); recruitment for this trial is expected to be finalized soon. Furthermore, a phase I study of lefitolimod in combination with the commercially available checkpoint inhibitor Yervoy (ipilimumab) in other solid tumors is being conducted in collaboration with MD Anderson Cancer Center, Texas. In addition, lefitolimod is also being investigated in a phase I study in HIV-infected patients (TEACH). Top-line results are expected in summer 2017.

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 (n=102). They were randomized in 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.

Small-cell lung cancer (SCLC)

Lung cancer is one of the most common cancers. The estimated number of new lung cancer cases per year is around 230,000 in the U.S. and in Europe more than 400,000 with an estimated number of deaths per year of approximately 170,000 and more than 350,000 respectively.

The two main types are non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). SCLC is a fast-growing type of lung cancer that usually spreads more quickly than NSCLC and represents approximately 15-20% of all lung cancer cases.

When first diagnosed, approx. 60-80% of SCLC-patients already have distant metastases or extensive local spreading of the disease called "extensive-disease" SCLC. The prognosis for extensive-disease SCLC is still very poor: median overall survival (OS) is less than 12 months and only few patients survive more than two years. Thus, there is a high unmet medical need for new treatment options.

For more information on the clinical development program including IMPULSE, IMPALA, the combination study, and TEACH please visit www.clinicaltrials.gov.

On April 24, 2017 Tiziana Life Sciences plc (AIM: TILS), a clinical stage biotechnology company developing targeted drugs for cancer and autoimmune diseases, reported the approval in Israel of a phase II clinical trial protocol for testing milciclib, a novel inhibitor of cell cycle dependent kinases (CDKs), in patients with refractory hepatocellular carcinoma ("HCC") (Press release, Tiziana Life Sciences, APR 24, 2017, http://www.tizianalifesciences.com/single-post/2017/04/24/Tiziana-Life-Sciences-Announces-Approval-of-a-Phase-II-Clinical-Trial-Protocol-for-Milciclib-in-Patients-with-Hepatocellular-Carcinoma [SID1234518675]). A similar clinical trial protocol has been submitted for approval in Italy, Turkey and Greece. The primary objective of these multi-centered, multi-country and dose-ranging phase IIa clinical studies is to evaluate the safety of milciclib in HCC patients who fail to respond or are intolerant to the existing standard of care treatment. First patient enrollment is expected next month and top line data from the trial is expected by Q3 2018.

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In previous clinical studies, oral treatment with milciclib was found to be safe and well-tolerated in patients with refractory solid tumours, thymoma and thymic cancers. Data from animal studies has demonstrated that oral administration with milciclib effectively suppressed tumour growth in mouse models of HCC. Although the precise mode of action is not clearly understood, the preclinical studies conducted strongly suggest that milciclib acts primarily through downregulation of microRNA (miR) 221 and 222, which are known to be associated with hepatocarcinogenesis. Overexpression of miR-221 and miR-222 is also believed to be associated with development of resistance to sorafenib (Nexavar) in HCC patients

Gabriele Cerrone, Chairman of Tiziana commented: "HCC is a real unmet medical need due to its growing incidence and lack of effective therapy. It is the fifth most common cancer worldwide and the second most common cause of death from cancer worldwide. We strongly believe that milciclib has the potential to be developed either as a monotherapy or in combination with sorafenib for treatment of HCC."

Dr. Yaron Ilan, Director of the Department of Medicine at Hebrew University Hadassah Medical Center, Israel and Chief Medical Officer of Tiziana added: "The prognosis for liver cancer is very poor due to lack of effective therapy. We were very encouraged with recent pre-clinical findings and are now moving forward to conduct a phase II clinical trial in HCC patients with milciclib in patients that failed to respond to the standard of care therapy. We believe that milciclib holds promise as an effective anti-cancer treatment with a high safety profile."

About HCC

Hepatocellular carcinoma is the fifth most common cancer in men and the ninth in women. Additionally, it is the fifth most common cancer worldwide and the second most common cause of death from cancer worldwide[1]. The tumour is associated with chronic hepatitis B and chronic hepatitis C infections, as well as with nonalcoholic steatohepatitis. The prognosis for liver cancer is very poor due to lack of effective therapy.


About Milciclib

Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases (CDKs) such as CDK1, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signaling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. Oral treatment with milciclib was found to be effective in reducing tumour growth in animal models of HCC, possibly through downregulation of miR-221 and miR-222. In a phase I study, oral treatment with milciclib was found to be well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in thymic carcinoma, pancreatic carcinoma and colon cancer.

On April 24, 2017 SillaJen, Inc., (KOSDAQ:215600), a clinical-stage, biotherapeutics company focused on the development of oncolytic immunotherapy products for cancer, and Transgene (Paris:TNG) (Euronext: TNG), a French biotechnology company focused on discovering and developing immune-targeted immunotherapies for the treatment of cancer and infectious diseases, reported that they have enrolled the first European patient in the ongoing multinational randomized Phase 3 open-label study of Pexa-Vec (formerly JX-594), in patients with advanced liver cancer, also known as hepatocellular carcinoma (HCC) (Press release, Transgene, APR 24, 2017, View Source [SID1234518674]). The trial is evaluating the use of Pexa-Vec to treat HCC patients who have failed locoregional therapies and are eligible for treatment with sorafenib (Nexavar), the only approved systemic treatment for advanced HCC. The European patient was enrolled at Azienda Ospedaliero-Universitaria Hospital in Parma, Italy.

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The enrollment of the first European patient triggers a $4 million USD milestone to be paid to SillaJen by Transgene.

The study, named the PHOCUS trial, started in January 2016 and is now active in North America, Asia, Australia and Europe. It is designed to enroll 600 patients who have not received prior systemic treatment for their cancer, and they will be randomized to one of two treatment groups: one which will receive Pexa-Vec followed by sorafenib and one which will receive sorafenib alone. The randomized study will be conducted at approximately 140 sites worldwide. SillaJen reached agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for this global Phase 3 clinical trial. The primary objective of the study is to determine the overall survival of patients treated with Pexa-Vec. Secondary objectives include safety as well as assessments for tumor responses between the two groups as measured by the following endpoints: time to progression, progression-free survival, overall response rate and disease control rate. To learn more about the trial, please visit: View Source

“We are pleased with the progress in our PHOCUS trial and are happy to report that we are now enrolling patients in 11 countries across the globe,” stated Eun Sang Moon, chief executive officer of SillaJen. “This trial, which is actively enrolling patients with HCC, is being conducted at some of the most highly regarded institutions for cancer in the world, and we are grateful to be working with such an exemplary team of physicians.”

“The enrollment of the first patient in Europe in the PHOCUS trial is an important step forward in the development of Pexa-Vec in association with the current standard of care in advanced liver cancer,” said Philippe Archinard, chairman and chief executive officer of Transgene. “This trial is part of a broad clinical development plan that will allow us to position this promising oncolytic virus in all relevant settings to improve the clinical outcome of patients with advanced solid tumors such as HCC, in which there still is a very high unmet medical need.”

At the Azienda Ospedaliero-Universitaria of Parma, a multidisciplinary team, coordinated by Dr. Gabriele Missale, collaborates to provide the best treatment decisions for patients with HCC. “Indeed we need new options for patients with advanced HCC and the immunotherapeutic approach with Pexa-Vec is a new weapon and a great opportunity for our patients. Having enrolled, here in Parma, the first European patient into the PHOCUS Trial, testifies our commitment to expanding options to fight HCC,” stated Dr. Missale.

Pexa-Vec Clinical Development Program and SOLVE Platform
Pexa-Vec is the most advanced product candidate from SillaJen’s proprietary SOLVE (Selective Oncolytic Vaccinia Engineering) platform. The vaccinia strain backbone of Pexa-Vec has been used safely in millions of people as part of a worldwide vaccination program. This strain naturally targets cancer cells due to common genetic defects in cancer cells; Pexa-Vec was engineered to enhance this by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express the immunogenic GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack.

On April 24, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that it has commenced a phase 2 trial to evaluate the efficacy of VGX-3100 in patients with pre-cancerous lesions of the vulva, or vulvar intraepithelial neoplasia (VIN) (Press release, Inovio, APR 24, 2017, View Source [SID1234518670]). VGX-3100 is an immunotherapy that targets human papillomavirus (HPV) 16 and 18 and is being studied for the treatment of HPV-related pre-cancerous lesions and persistent HPV infection that causes these lesions.

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VIN has a very low rate of spontaneous, or natural, regression − below 5%. Currently there are no FDA approved non-surgical treatments for pre-cancerous lesions of the vulva. Surgery, the most common treatment, is associated with high rates of disease recurrence and can cause disfigurement, long-term pain, and psychological distress for the women who undergo the procedure. VIN recurs in approximately one of every two patients who undergo surgical treatment.

This randomized, open label phase 2 study will assess the efficacy of VGX-3100 in 36 women with high-grade HPV-related vulvar lesions. The immunotherapy will be administered with Inovio’s CELLECTRA intramuscular delivery device. The primary endpoint of the study is histologic clearance of high-grade lesions and virologic clearance of the HPV virus in vulvar tissue samples. The study will also evaluate safety and tolerability of VGX-3100.

Inovio’s immunotherapy aims to address the unmet medical need for VIN by providing a non-surgical option for women with this disease. In a previously conducted phase 2b randomized, placebo controlled study of 167 women with HPV-associated cervical pre-cancer, VGX-3100 led to a significantly higher rate of lesion regression and clearance of the underlying HPV viral infection. Inovio plans to initiate a phase 3 study of VGX-3100 as a treatment for high grade cervical dysplasia in 2017, and the treatment of VIN represent an important additional indication for its lead product.

Dr. Robert Edwards, Chair of Obstetrics and Gynecology at the University of Pittsburgh School of Medicine at Magee-Women’s Hospital and Professor of Medicine in the Department of Obstetrics, Gynecology, and Reproductive Sciences at the University of Pittsburgh, School of Medicine, said, "HPV-induced VIN is one of the major causes of morbidity for young and middle-aged women with HPV-induced pre-cancer. It is associated with repetitive need for surgery, multiple biopsies, and a major cause of pain and sexual dysfunction."

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "Inovio’s VGX-3100 may provide the first approved non-surgical treatment option for women with this HPV-related pre-cancer with a high recurrence rate. My optimism is based on our phase 2b efficacy results finding clearance of lesions and the HPV virus in many subjects in our evaluation of VGX-3100 in women with high grade cervical dysplasia. Our ultimate goal is for VGX-3100 to become the "go-to" immunotherapy to treat all major HPV-related premalignant diseases."

About Vulvar Pre-Cancers

If left untreated vulvar pre-cancers can progress to invasive cancer of the vulva. Approximately 27,000 cases of HPV-related vulvar pre-cancers occur in the U.S. each year and about 12,000 to 24,000 cases in Europe each year. HPV-16 and/or HPV-18 are involved in about 80% of HPV-related vulvar pre-cancers cases in the U.S. and Europe. Once vulvar pre-cancers develop, spontaneous regression (i.e. natural disappearance of the lesion) is rare and occurs in 1.5% to 5% of cases. An estimated 6,000 new cases of vulvar cancer occur in the U.S. each year with about 50% to 80% of those being HPV-associated. About 1,110 deaths occur annually due to vulvar cancer in the U.S. Standard of care treatment of vulvar pre-cancer usually involves surgery, which has significant physical and psychosocial impacts in women (e.g. severe pain, disfigurement, sexual dysfunction), and the success of such surgery is marginal, as the recurrence rate of high grade vulvar pre-cancer is extremely high, i.e. about 50% three years post-treatment.

About VGX-3100

VGX-3100 is an HPV-specific immunotherapy that is being developed as a non-surgical treatment for high-grade HPV-caused pre-cancers and other related underlying persistent HPV infections. VGX-3100 works in vivo to activate functional, antigen-specific, CD8 killer T-cells to clear persistent HPV infection and cause regression of pre-cancerous lesions. In a phase 2 trial to treat cervical dysplasia, VGX-3100 demonstrated clinical efficacy and was generally well tolerated, without the side effects and obstetric risks associated with surgical excision. VGX-3100 is a first-in-class HPV-specific immunotherapy that targets the underlying cause of HPV-related pre-cancers, providing an opportunity for women to reduce their risk of cervical cancer without undergoing an invasive surgical procedure.

On April 24, 2017 PDL BioPharma, Inc. (PDL or the Company) (NASDAQ: PDLI) reported that on April 21, 2017, the Company entered into a settlement agreement with certain subsidiaries of Merck & Co., Inc. ("Merck") to resolve the patent infringement lawsuit between the parties pending in the U.S. District Court for the District of New Jersey related to Merck’s Keytruda humanized antibody product (Press release, PDL BioPharma, APR 24, 2017, View Source [SID1234518669]). Under the terms of the agreement, Merck will pay the Company a one time, lump-sum payment of $19.5 million, and the Company will grant Merck a fully paid-up, royalty free, non-exclusive license to certain of the Company’s Queen et al. patent rights for use in connection with Keytruda as well as a covenant not to sue Merck for any royalties regarding Keytruda. In addition, the parties agreed to dismiss all claims in the relevant legal proceedings.

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"We are pleased to resolve this patent infringement lawsuit with Merck with a favorable monetary settlement to PDL as well as eliminating potential future litigation costs related to this matter for both parties," said John P. McLaughlin, president and chief executive officer of PDL. "As a result of this settlement, we expect to recognize $19.5 million in license revenue for the second quarter ending June 30, 2017."