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Latest news

Ignyta announces phase 1 clinical trial data for Entrectinib
Nerviano, June 1, 2015 - Well tolerated, with no drug-related serious adverse events. Recommended phase 2 dose determined. 91% response rate in patients meeting expected phase 2 eligibility criteria  (see Ignyta press release).
Nerviano Medical Sciences: new personalized treatments active on acute myeloid leukemia, gastrointestinal and female tumors, with innovative...
Nerviano, April 21, 2015 - Efficacy in leukemia with no cardiotoxicity or ‘gatekeeper’ mutation resistance for NMS-P088. Several opportunities among PARP-1 inhibitors, active in breast and aovary tumors with BRCA1 e BRCA2 mutation. Presented the establishment and characterization of a chordoma cell line, relevant for the knowledge of this rare cancer and the research of new therapies.

Nerviano Medical Sciences presented at the American Association for Cancer Research annual meeting in Philadelphia efficacy and tolerability data of new candidates treatments of acute myeloid leukemia and gastrointestinal, breast and ovary cancer, acting as potent inhibitors of tumor cells growth through specific molecular targets.

The molecule NMS-P088 - developed entirely in Nerviano laboratories - is a potent and selective inhibitor of both kinases FLT3 and KIT, whose mutations are involved in the pathogenesis of acute myeloid leukemia (AML), gastrointestinal stromal tumors (GIST), as well as other solid tumors including specific melanoma subtypes.

Nerviano Medical Sciences commitment in research new treatments for acute myeloid leukemia is answering to an important unmet clinical need. In fact, no therapeutic treatments for AML are approved for patients, often young people, presenting the FLT3 kinase constitutively activated and not responding to chemotherapy.
On this regard, new evidences presented at Philadelphia show that in this disease NMS-P088 has an excellent and selective inhibitory activity of tumor growth, associated to a good tolerability profile and a good synergy with chemotherapy that suggest, therefore, a possible and more effective combination with standard chemo treatments.

In GIST NMS-P088 has demonstrated to be more active and powerful, even at lower doses, than current approved treatment.

On the whole, the profile of NMS-P088 has showed to not generate cardiotoxicity including QT prolongation and to not develop resistance to ‘gatekeeper’ mutation (as usually occurs in patients presenting this specific mutation, becoming resistant to all kinase inhibitors approved).
Studies, preparatory for clinical phase beginning, are being completed.

A further research line of Nerviano Medical Sciences presented at AACR meeting is related to PARP enzyme inhibitors, which are involved in the replication and reparation of DNA, also effective, for example, in the treatment of breast and ovary tumors with BRCA1 and BRCA2 mutation.

Among these inhibitors, those active for PARP-1 and able to not inhibit simultaneously PARP-2 are resulting more effective in terms of better ‘Time To Progression’, thanks to their excellent pharmacokinetic profile. Moreover they show a better toxicity profile compared to the only one currently approved for relapsing BRCA ovarian cancer.

Studies on different origin cell lines, including those with the BRCA mutation and those resistant to standard chemotherapy, indicate also a unique activity profile of these inhibitors that can suggest further innovative therapeutic opportunities linked to DNA repair processes.
On this regard, translational and bioinformatics studies are in progress aiming to identify further sensitivity to the activity of these selective inhibitors and related specific patients populations.

During the event, scientists have also presented an important case of stabilization and characterization of a chordoma cell line, realised at Nerviano laboratories in collaboration with the National Cancer Institute of Milan, a worldwide excellence for the treatment of this rare bone tumor, for which there are no approved drug therapies.
In this context, a new stabilized cell line will allow to better understand and study this rare cancer and to test quickly and optimally the activity and efficacy of new molecules, understanding at the same time their mode of action.

Reference
Establishment and characterization of the new sacral chordoma cell line Chor-IN-1
Authors: Paola Magnaghi et al
Meeting: AACR Annual Meeting 2015, Abstract number 74
Presentation Time: Sunday, Apr 19, 2015, 1:00 PM - 5:00 PM

NMS-P088, a dual FLT3-KIT inhibitor active also on gatekeeper mutations and devoid of QTc prolongation
Authors: Ciomei, M et al
Meeting: AACR Annual Meeting 2015, Abstract number 798
Presentation Time: Sunday, Apr 19, 2015, 1:00 PM - 5:00 PM

Preclinical characterization of the novel TTK kinase inhibitor S81694 for the treatment of triple negative breast cancer
Authors: Riccardo Colombo et al
Meeting: AACR Annual Meeting 2015, Abstract number 1638
Presentation Time: Monday, Apr 20, 2015, 8:00 AM -12:00 PM

Preclinical characterization of NMS-P648, a novel and potent PARP-1/-3 inhibitor
Authors: Alessia Montagnoli et al
Meeting: AACR Annual Meeting 2015, Abstract number 2851
Presentation Time: Monday, Apr 20, 2015, 3:50 PM - 4:05 PM
Oral presentation: PARP and DNA Repair Inhibitors (Minisymposium)
Session Start/End Time: Monday, Apr 20, 2015, 3:00 PM - 5:00 PM
Location: Room 108, Pennsylvania Convention Center
SOT 2015: presented by Accelera and StemGen new data on treatment of glioblastoma, the most common brain tumor.
Nerviano, March 27, 2015 - Under study toxicity and safety profile of a new treatment designed with BMP4 of stemgen, a 'key' protein able to block the reproduction of stem cells in brain tumor. The results of pre-clinical reasearch show a good toxicity profile and suggest BMP4 as a possible innovative biological therapy against the most aggressive and resistant of brain tumors.

The administration of BMP4 in preclinical – in intracerebral or intravenous infusion over a period of 7 days - has showed good tolerability with no particular effects of local or systemic toxicity. These results were presented by Nerviano researchers at SOT 2015 in San Diego, the 54th annual meeting of the Society of Toxicology.

The relationship between glioblastoma growth and cancer stem cells has been already extensively studied by Prof. Angelo Luigi Vescovi and his team at StemGen in Milan. These stem cells are responsible for the growth of many tumors, including glioblastoma and are difficult to isolate and hit as they escape traditional oncology therapies. Cancer stem cells are also responsible for relapses of this tumor, absolutely the most lethal ones.


Thanks to its toxicological research, Accelera - of NMS Group - contributed to the development of the innovative therapeutic approach based on BMP4. As already reported by StemGen on Nature in 2006, this morphogenetic protein is able to force the mutation of glioblastoma stem cells into more differentiated nerve cells, unable to continue the disease growth. The concept is radically new and never conceived up to now in solid tumors.


“Manage to neutralize the 'bad' stem cells of glioblastoma
- sayd Professor Vescovi, Founder and Scientific Director of StemGen Spa - means to inhibit the tumor growth and also to reduce the relapse risk for this relevant cancer with a frequent lethal prognosis. Today BMP4 represents a hope and an important candidate treatment that has already received recognition as Orphan Drug by the European regulatory authorities.”

Glioblastoma is the most frequent and high malignant form of primary tumors affecting the central nervous system and represents 15% of all brain tumors. According to Italian Association of Cancer Registries (Airtum) data, in our country it affects over 1,200 people per year, on average between 45 and 70 years even if it has a youth and pediatric peak. In fact, glioblastoma is the most frequent histological type among rare pediatric brain tumors, with a lethal prognosis.
The average survival is unfortunately less than two years.


New data from preclinical toxicology phase presented by researchers of Accelera - among the few companies involved in preclinical research activities in Italy - and StemGen confirm that the administration of BMP4 could represent in the future a potential innovative therapy for this aggressive and resistant brain tumor.


“The research project developed for StemGen
- adds Enrico Pesenti, Managing Director of Accelera - confirms the exclusive expertise of Accelera as partner of major international players and public and private institutions involved in developing preclinical programs of biological and advanced cell therapies. Furthermore, it recognises the quality and the excellence of the research developed in Nerviano laboratories.”
Preclinical results are more than encouraging, now it's up to clinical phase trials to confirm the effectiveness of this new biological treatment.

Reference

http://www.stemgen.net
S. G. M. Piccirillo, B. A. Reynolds, N. Zanetti, G. Lamorte, E. Binda, G. Broggi, H. Brem, A. Olivi, F. Dimeco and A. L. Vescovi. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumor-initiating cells. Nature 444, 761-765 (7 December 2006)
G. Di Gallo, L. Nobili, M. Russo, E. Binda, C.I. Bernardi; A.L. Vescovi Human-recombinant Bone Morphogenetic Protein 4 (hrBMP4): Safety profile  after 7-day continuous Intracerebral (IC) and IV Administration in the mouse (Poster presentation, SOT 2015)
Four presentations from Nerviano Medical Sciences at the 2015 AACR meeting

Nerviano,  March 18, 2015 - Nerviano Medical Sciences will present four posters, one selected for an oral presentation, at the American Association for Cancer Research (AACR) Annual Meeting 2015, April 18 - 22, 2015, Pennsylvania Convention Center, Philadelphia, Pennsylvania.

Presentation title: Establishment and characterization of the new sacral chordoma cell line Chor-IN-1
Authors: Paola Magnaghi et al
Meeting: AACR Annual Meeting 2015, Abstract number 74
Presentation Time: Sunday, Apr 19, 2015, 1:00 PM - 5:00 PM



Presentation Title: NMS-P088, a dual FLT3-KIT inhibitor active also on gatekeeper mutations and devoid of QTc prolongation
Authors: Ciomei, M et al
Meeting: AACR Annual Meeting 2015, Abstract number 798
Presentation Time: Sunday, Apr 19, 2015, 1:00 PM - 5:00 PM


Presentation title: Preclinical characterization of the novel TTK kinase inhibitor S81694 for the treatment of triple negative breast cancer
Authors: Riccardo Colombo et al
Meeting: AACR Annual Meeting 2015, Abstract number 1638
Presentation Time: Monday, Apr 20, 2015, 8:00 AM -12:00 PM


Presentation title: Preclinical characterization of NMS-P648, a novel and potent PARP-1/-3 inhibitor
Authors: Alessia Montagnoli et al
Meeting: AACR Annual Meeting 2015, Abstract number 2851
Presentation Time: Monday, Apr 20, 2015, 3:50 PM - 4:05 PM


The last poster has been selected for an oral presentation:
Session title: PARP and DNA Repair Inhibitors
Session type: Minisymposium
Session Start/End Time: Monday, Apr 20, 2015, 3:00 PM - 5:00 PM
Location: Room 108, Pennsylvania Convention Center


The full abstracts can be found on the conference website: http://www.aacr.org

Rector of the University of Milan visiting Nerviano Campus
Nerviano, January 23, 2015 - Prof. Gianluca Vago, Rector of the University of Milan, was today guest at the laboratories and facilities of NMS Group.

The visit - has declared the Rector - originates from the will to deepen the knowledge of a research and development company that already cooperates with the University and that maintains specific characteristics on the national landscape.”

Linking the biology and the chemistry approach, Campus activities are focused on new molecules discovery that aim to become the cancer care of the future. In fact, NMS Group is an integrated organization able to manage the entire path of new drugs research and development, from pre-clinical phase to product production.

In the Campus are evident the scientific heritage - continued the Rector – the expertise in the area and some particular specificities in few research line.”
In fact, the Campus in Nerviano is today an excellence in the research field, characterized by innovative technologies and a great historic scientific know-how that joint together in the exclusive scientific platforms at the basis of new personalized therapies development.

There are definitely the conditions - concluded Prof. Vago - to extend the current collaboration, both in scientific and training areas, for a mutual sharing of reciprocal expertise.”
Tiziana Life Sciences licenses milciclib from Nerviano Medical Sciences
London, January 20, 2015 - Tiziana Life Sciences plc (“Tiziana”, “the Company”, AIM: TILS), the clinical stage biotechnology company focused on targeted drugs to treat diseases in oncology and immunology, is pleased to announce that it has exclusively licensed milciclib from Nerviano Medical Sciences Group (“Nerviano”), an Italian company dedicated to the discovery and development of breakthrough treatments for cancer.

Milciclib blocks the action of specific enzymes called cyclin-dependent kinases (“CDKs”), which are involved in cell division as well as a number of other protein kinases. Milciclib is currently in phase II clinical trials for thymic carcinoma in patients previously treated with chemotherapy. Milciclib has demonstrated that it is well tolerated in over 263 patients in phase I and II clinical trials and has been granted orphan designation by the European Commission and by the U.S. Food and Drug Administration (“FDA”) for the treatment of malignant thymoma / thymic epithelial tumours. Subject to successful completion of the ongoing phase II trials, Tiziana is committed to initiate a phase III study in this indication in 2016.

Nerviano has shown in preclinical studies that milciclib has potential in other cancer indications, in particular liver cancer and breast cancer, for which potential biomarkers of response have been identified and which will support the clinical development in these indications planned to start in 2015. Tiziana plans to immediately enrol patients into a new phase II trial in hepatocellular carcinoma using a protocol already prepared by Nerviano, and will explore the potential for an additional phase II trial in breast cancer.

Commenting on the licensing agreement, Gabriele Cerrone, Chairman and Founder of Tiziana, said: “Nerviano is a high value partner for Tiziana with immense scientific heritage in oncology that started with the success of the anthracyclines and is now continuing with innovative targeted therapies. The addition of milciclib, with its robust safety profile, significantly strengthens Tiziana’s pipeline and offers us the potential to provide a new treatment for liver cancer, an additional approach for treating breast cancer and continuing phase II trials in thymic carcinoma. Milciclib broadens our breast cancer franchise and, together with foralumab, which we licensed in late 2014, we now have two clinical assets with three different clinical indications.”

Under the terms of the licensing agreement with Nerviano, Tiziana will make an upfront cash payment of US$3.5 million for the license to Nerviano. Tiziana will also pay to Nerviano specified milestone payments of up to US$35 million and a royalty on net sales of any products containing milciclib.

In addition, Tiziana will pay £2.14 million to be satisfied by the issue of 4,233,616 new ordinary shares (the "Shares") in the Company to Nerviano (at a price of 50.5p per share which is the closing price of the Company’s ordinary shares on 16 January 2015, the last business day prior to execution of the licensing agreement). The Shares are subject to restrictions dependent on the success of the clinical development programmes. In the event that there is an unsuccessful phase II trial in liver cancer or breast cancer, or a phase II trial has not been completed by 19 January 2020, the Company has the right to buy back the Shares for a consideration of £1. Nerviano has agreed that the Shares will be subject to a lock-in arrangement until successful completion of a phase II trial and for a period of 12 months thereafter. Nerviano will be able to exercise voting rights relating to the Shares whilst they are locked in.

Application has been made to the London Stock Exchange for the Shares to be admitted to trading on AIM which is expected to occur on or around 26 January 2015. Following the issue of the Shares, the Company will have 88,905,928 ordinary shares in issue. The Shares will rank pari passu with the existing ordinary shares of the Company. Exercise of the Company's buy back rights is subject to shareholder approval under the UK Companies Act and is expected to be obtained at the Company's annual general meeting in 2015.

Under the licensing agreement, Tiziana will be responsible for future development costs for milciclib in thymoma / thymic epithelial tumours and in any additional indications, including hepatocellular carcinoma and breast cancer. Tiziana will entrust the manufacturing and the performance of clinical studies for milciclib up to completion of phase II to Nerviano.

We are delighted to enter into this agreement with Tiziana Life Sciences, as a further recognition of our research approach and the value of our pipeline,” said Luciano Baielli, CEO of Nerviano. “As a group, Nerviano is, in fact, actively building alliances to strengthen the development of our projects and offer new therapeutic options for physicians and patients’ unmet needs. Our goal is to lead innovation in oncology and I am confident that our recognised expertise as a provider of integrated R&D capabilities will lead to a further significant new hope for cancer patients."

About Tiziana Life Sciences

Tiziana Life Sciences plc is a UK biotechnology company that focuses on the discovery and development of novel molecules that treat human disease in oncology and immunology.

The Company has a phase II asset, foralumab, the only fully human engineered anti-human CD3 antibody in clinical development. Foralumab has potential application in a wide range of autoimmune and inflammatory diseases, such as multiple sclerosis, type-1 diabetes (T1D), inflammatory bowel disease (IBD), psoriasis and rheumatoid arthritis, where modulation of a T-cell response is desirable.

Tiziana Life Sciences’ research team has discovered that Bcl-3 has a prominent role in the metastasis of mammary cancers, and has elucidated the mechanism of Bcl-3 action to be a regulator of cancer cell motility. Tiziana has also determined that Bcl-3 inhibition suppresses cell motility in triple-negative, HER-2-positive PR- and ER-positive breast cancer sub-types, suggesting that Bcl-3 may be a master regulator of this metastatic property not only in aggressive breast cancers, but across the clinical spectrum of breast disease.

   
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