On October 13, 2017 Impact Biomedicines ("Impact") reported its launch to pioneer the development of life-changing treatments for patients with myeloproliferative neoplasms and other cancers (Press release, Impact Biomedicines, OCT 13, 2017, View Source [SID1234520974]). The Company’s pipeline is centered around fedratinib, a potent and highly selective oral small molecule JAK2 kinase inhibitor that is being developed initially for the treatment of myelofibrosis (MF) and polycythemia vera (PV). In conjunction with this launch, Impact is pleased to share that the U.S. Food and Drug Administration (FDA) has removed the clinical hold placed on fedratinib and that the company has received $22.5 million from Medicxi through a Series A financing.

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Impact was formed in 2016 after acquisition of Sanofi’s full rights for the global development and commercialization of fedratinib. The majority equity holders in Impact include the co-founders and Medicxi, with Sanofi retaining a minority stake.

In 2013, the development of fedratinib was discontinued by Sanofi after the FDA issued a clinical hold subsequent to reports of a few potential cases of Wernicke’s encephalopathy (WE), an acute neurological condition usually indicative of a vitamin B deficiency, in patients participating in fedratinib clinical trials. Following a Type A meeting and review of additional data, the FDA concluded that Impact provided the necessary documentation to support lifting the clinical hold – opening the path for Impact’s continued development of fedratinib.

The clinical package for fedratinib includes data from a total of 18 studies completed in 877 subjects. In JAKARTA-1, a completed international Phase 3 pivotal trial for the treatment of myelofibrosis, fedratinib met its primary and secondary endpoints by reducing spleen size in 47% of patients by ≥35% at 24 weeks (p<0.0001) and improving symptom score in 36% of patients by ≥50% at 24 weeks (p< 0.0001). Comparable responses were seen in patients with normal or low platelet counts and thrombocytopenia was similar between placebo and the target dose of 400mg. In JAKARTA-2, a follow-on study in patients who were unresponsive to all other available therapies, including patients who were either Jakafi (ruxolitinib) resistant or intolerant, fedratinib showed similar activity. In that study, 55% of patients who had failed or were intolerant to ruxolitinib experienced a spleen size reduction of ≥35% with fedratinib. Notably, responses were noted in 63% of patients intolerant to ruxolitinib and 61% of patients who had lost ruxolitinib response. Currently, ruxolitinib is the only drug approved by the FDA to treat patients with MF and PV. The most common adverse events for fedratinib were hematological (anemia) and gastrointestinal (nausea, diarrhea and vomiting). The results of these trials have been published in leading peer-reviewed journals.

"The decision to discontinue the development of fedratinib in 2013 was heartbreaking for the patients who were experiencing positive responses while in clinical trials. There are very limited therapeutic options for these patients and fedratinib was active in most patients when nothing else had worked. Because of the very high unmet medical need in MF, the Impact team completed a thorough review of the available data, including careful due diligence into the potential cases of WE and I am glad to report that as a result of this effort, the FDA has lifted the clinical hold," said John Hood, Ph.D., Chief Executive Officer of Impact. "In addition to MF, Impact intends to pursue multiple clinical indications for fedratinib to realize its potential as a best-in-class JAK2 kinase inhibitor."

To support the Company’s drug development and manufacturing efforts and the build out of the management team, Impact closed a $22 million Series A financing with Medicxi.

"We’ve made it a point to double down and invest more in maturing life science companies who are delivering innovation where it’s needed most. In line with our ‘asset-centric’ approach, we believe Impact is doing just that by reviving fedratinib with a thoughtful development approach and due diligence," said Kevin Johnson, Impact board member and Co-Founder of Medixci. "We are confident that the dedicated team at Impact has the vision and skill to create a sustainable long-term business around fedratinib."

The development of fedratinib is being led by a highly skilled and devoted team, including members of the original TargeGen team, where fedratinib was first developed prior to its acquisition by Sanofi.

Dr. Hood serves as Chief Executive Officer of Impact Biomedicines. Prior to founding Impact, he was co-founder and Chief Scientific Officer of Samumed, a pharmaceutical platform company focused on advancing regenerative medicine and oncology applications. Prior to that, Dr. Hood was Director of Research and co-inventor of fedratinib at TargeGen, Inc., (subsequently acquired by Sanofi SA), where he led a team identifying small molecule kinase inhibitors for the treatment of eye diseases and cancer. He is an inventor on 100+ patents and author on 50+ scientific articles. Dr. Hood obtained a Ph.D. in medical physiology and B.S. in biochemistry from Texas A&M University.

Dr. Catriona Jamieson serves as Interim Chief Medical Officer of Impact Biomedicines, and co-founder. Concurrently, Dr. Jamieson is a Professor of Medicine and Chief of Regenerative Medicine, Deputy Director of the Sanford Stem Cell Clinical Center, Co-leader of the Hematologic Malignancies Program, and Director of Stem Cell Research at the Moores UC San Diego Cancer Center. She specializes in myeloproliferative neoplasms and leukemia, and was the principal investigator on several fedratinib trials. Dr. Jamieson obtained an M.D., a Ph.D. in microbiology and a B.S. in Genetics from the University of British Columbia prior to completing fellowships in hematology and bone marrow transplantation at Stanford University and being recruited to UC San Diego.

About Myeloproliferative Neoplasms
Myeloproliferative Neoplasms (MPN) are a closely-related group of blood cancers in which the body, specifically the bone marrow, makes too many red blood cells, platelets, or certain white blood cells. There are three types of blood cancers that comprise MPNs: Myelofibrosis, Polycythemia Vera and Essential Thrombocythemia. MPNs are characterized by the mutations of JAK2, MPL o

Transgene (Paris:TNG), a biotech company that designs and develops viral-based immunotherapies, recently published two papers supporting the efficacy and mechanism of action of its therapeutic vaccine TG4010 (Press release, Transgene, OCT 12, 2017, View Source [SID1234520883]). After successful completion of the phase 2b TIME trial for combination of TG4010 and chemotherapy (Quoix et al. Lancet Oncol., 2015), these two peer-reviewed articles support the ongoing development of the product in combination with immune checkpoint inhibitors (ICIs) in advanced NSCLC. More generally, they confirm the interest in viral vectors as immunotherapeutics.

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In this paper, based on samples from 78 patients of the TIME trial, Transgene provides the first data linking directly the development of a specific cellular immune response with an improved clinical benefit in patients with advanced NSCLC upon vaccination with a viral vector.
It was shown that the significantly longer overall survival (OS) of patients treated with TG4010 is correlated with the diversity and intensity of CD8+ T cell responses against the MUC1 antigen.
Treatment with TG4010 also led to a broadening of immune response to other tumor-associated antigens that were not targeted by the vaccine. This is the first report of such a mechanism of epitope spreading for a virus-based immunotherapeutic product. This spreading might contribute to the enrichment of the diversity of the anti-cancer response.
These results support the causality of T-cell response in improved survival in NSCLC, and strengthen the rationale for combination with ICIs to exploit the broad CD8+ T cell repertoire induced by TG4010 vaccination.

"Sequential administration of MVA-based vaccines and PD-1/PD-L1-blocking antibodies confers measurable benefits on tumor growth and survival: preclinical studies with MVA-βGal and MVA-MUC1 (TG4010) in a murine tumor model." By Remy-Ziller et al., Human Vaccines & Immunotherapeutics, 2017 Sep (19:0), doi: 10.1080/21645515.2017.1373921. epub ahead of print

Transgene further demonstrates the benefit of administration of MVA-vaccines, and ICIs in a preclinical metastatic model. Treatment with MVA vectors showed increased survival rates, and led to the accumulation of CD3dimCD8dim T cells in the lung and an upregulation of PD-1 was observed on these T cells.
Targeting the PD-1/PD-L1 pathway with ICIs in association with TG4010 treatment, at late stage of tumor development, enhanced the therapeutic activity induced by the vaccine, supporting the two ongoing clinical evaluation of TG4010 in combination with nivolumab.

About TG4010
TG4010 is an immunotherapy that has been designed to express the coding sequences of the MUC1 tumor-associated antigen and the cytokine, Interleukin-2 (IL2) in a modified vaccinia virus (MVA).
The combination of TG4010 immunotherapy and chemotherapy has demonstrated significant efficacy in terms of progression-free survival and overall survival in patients with advanced stage NSCLC (Quoix et al. Lancet Oncol. 2015). TG4010 is currently being investigated in combination with nivolumab (ICI) for the 2nd-line treatment of advanced NSCLC (NCT02823990). A trial in 1st-line treatment of NSCLC is expected to begin at the end of 2017, evaluating the combination regimen of TG4010 + nivolumab + chemotherapy in patients whose tumors express low or undetectable levels of PD-L1.

On October 12, 2017 – Shire plc (LSE: SHP, NASDAQ: SHPG), reported that it will announce third quarter 2017 earnings on Friday October 27, 2017 (Press release, Shire, OCT 12, 2017, View Source [SID1234520888]).

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Results press release will be issued at: 12:00 BST / 07:00 EDT
Investor conference call time: 14:00 BST / 09:00 EDT

Live conference call for investors:
Flemming Ornskov, MD, Chief Executive Officer, Jeff Poulton, Chief Financial Officer and Matt Walker, Head of Technical Operations will host the investor and analyst conference call at 9:00 EDT / 14:00 BST.

The details of the conference call are as follows:
UK dial in: 0808 237 0030 or 020 3139 4830
US dial in: 1 866 928 7517 or 1 718 873 9077
International Access Numbers: Click here
Password/Conf ID: 31097524#
Live Webcast: Click here

Replay:
A replay of the presentation will be available for two weeks by phone and by webcast for three months. Replay information can be found on the Investor Relations section of Shire’s website at View Source

For further information please contact:
Investor Relations
Ian Karp [email protected] +1 781 482 9018
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On October 11, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that it has entered into an agreement to collaborate with the University of Bergen to expand research on inhibition of brain metastasis by Moleculin’s pre-clinical drug WP1066 and its unique ability to increase immune system response to cancer and suppression of tumor cell proliferation and survival (Press release, Moleculin, OCT 11, 2017, View Source [SID1234520865]).

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"We’ve seen promising evidence that WP1066 has potent anticancer effects in animal tumor models due to its unique mode of action," commented Walter Klemp, Chairman and CEO of Moleculin. "WP1066 is well known for its ability to block the expression of the key oncogenic transcription factors that promote tumor growth and suppress immune system responses. As such, we believe WP1066 has promising potential to stimulate patients’ natural immune response against tumors."

Mr. Klemp continued: "We announced last month a separate collaboration with the University of Bergen in Norway on WP1122 for brain tumors. The WP1066 project will be led by Dr. Frits Alan Thorsen and may provide critical insight on WP1066, which we anticipate will be in clinical trials soon."

The Company previously announced that Moleculin is working with MD Anderson in their effort to move forward with a physician sponsored IND (Investigational New Drug) application to study WP1066 in patients with glioblastoma and melanoma that has metastasized to the brain. That IND has been on hold pending responses to requests from the FDA. If the FDA allows the IND to proceed based on the responses provided, Moleculin anticipates this clinical trial could be ready to begin by the end of this year.

On October 11, 2017 Janpix Inc., a privately held biopharmaceutical company dedicated to the discovery and development of inhibitors targeted to Signal Transducer & Activator of Transcription (STAT) proteins, reported that it has closed a US $19M investment round led by Medicxi, a GSK and J&J backed venture fund, which initially seeded the company (Press release, Janpix, OCT 11, 2017, View Source [SID1234530950]).

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Armed with a new understanding of how these proteins can simultaneously impact tumors as well as the tumor micro-environment, the company is advancing selective, small molecule inhibitors of STAT proteins, originally discovered at the University of Toronto Mississauga (UTM), towards clinical development.

STAT proteins, in particular STAT 3 and STAT 5, play a key role in regulating cell cycle, apoptosis, and proliferation, and it is widely recognized that their up-regulation is implicated in a number of solid and hematological cancers. More recent research suggests that inhibition of STAT proteins has also a profound impact on the tumor microenvironment, which offers the potential for these inhibitors to have a dual impact on tumors.

Until now, though, STAT proteins remained a hard-to-crack molecular target as intracellular protein-protein interactions are notoriously difficult to inhibit with small molecules. Previous efforts in this field have often resulted in either non-selective compounds or compounds binding to upstream targets. Using technologies and new chemistry developed by Prof Patrick Gunning, the Canada Research Chair in Medicinal Chemistry and a co-founder, Janpix has now been able to discover highly potent and selective STAT3 and STAT5 inhibitors, as well as pan-STAT3/5 inhibitors. With selective compounds in hand, the hope is that these targets can now be further investigated in the clinic.

"Immunotherapy is one of the biggest advances in cancer therapy in recent decades but it doesn’t work in a significant number of patients," said Roman Fleck, PhD, founding CEO of Janpix and an advisor to Medicxi. "By targeting the tumor directly along with its microenvironment we may be able to expand the universe of patients that can benefit from immunotherapies."

"It is exciting to see such an investment, which will translate academic concepts into practical applications," said Professor Ulrich Krull, UTM’s Vice-President and Principal. "These innovations in chemistry that have been pioneered at UTM will potentially support a better quality of life, and perhaps even save lives, for many patients in Canada and around the world."

"We are excited to continue supporting Janpix and Prof Gunning’s work on STAT inhibitors," said Giovanni Mariggi, PhD, a Principal at Medicxi and Board Member of Janpix. "Janpix has made great progress in developing tractable compounds that inhibit these difficult-to-target proteins. The role of STATs in multiple tumor types is supported by vast data and the emerging evidence of their role in tumor immunity adds an extra dimension to the potential impact these new drugs could have on patients."