On December 12, 2018 Apexian Pharmaceuticals reported is shedding light on the question of how pre-leukemic cells transform into full-blown leukemia (Press release, Apexian Pharmaceuticals, DEC 12, 2018, View Source [SID1234532134]).

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Genetic mutations by themselves are rarely enough to flip the switch. Inflammation also plays a role. But, until now, the question of "how" remained unanswered.

Apexian Chief Science Officer Mark Kelley, PhD, and his colleagues presented their findings at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s December 1, 2018 meeting in San Diego, California. When a putative tumor-suppressor gene called TET2 does not function well, acute inflammation or infection can enhance the production of myeloid stem and progenitor cells in the bone marrow that are precursors to circulating mature myeloid cells. The TET2 loss of function amplifies; inflammatory proteins increase, and myeloid cells rapidly mature, increasing in sheer numbers as well as developing resistance to programmed cell death.

Myeloid cells, which contribute to immunity, are normally very short-lived. However, when those cells live too long or become too numerous, dangerous levels of inflammation can result. Using a mouse model, Kelley and his colleagues demonstrated that Apexian’s flagship compound APX3330 can prevent precancerous cells from proliferating and block cells from making inflammatory proteins.

Such anti-inflammatory therapy could be of clinical value in people carrying TET2 mutations.

"Apexian continues to develop a robust portfolio of APE1/Ref-1 compounds that have broad utility in oncology, hematology and other diseases", says Steve Carchedi, President and CEO. "We are excited by the recent scientific findings and continue to expand our research and development beyond solid tumors"

APX3330 also has clinical utility with solid tumors. A Phase 1 trial for patients with advanced solid tumors is concluding.

On December 12, 2018 Checkmate Pharmaceuticals Inc., a clinical stage biopharmaceutical company focused upon activation of innate immunity to treat advanced cancer, reported that it has appointed Barry Labinger as President and CEO. Arthur M. Krieg, MD, Checkmate’s founder and current President and CEO, will assume the newly-created role of Chief Scientific Officer (Press release, Checkmate Pharmaceuticals, DEC 12, 2018, View Source [SID1234532035]). Both Mr. Labinger and Dr. Krieg will serve on Checkmate’s Board of Directors.

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Checkmate also announced the completion of a $22 million financing led by a new investor, Decheng Capital. The financing also included participation from existing investors, Sofinnova, venBio, and F-Prime.

"Checkmate’s encouraging early clinical data provide a strong foundation for its further growth as a leading cancer immunotherapy company with broad potential. Barry’s deep experience in oncology drug development and commercialization, along with this additional funding, will support Checkmate’s further progress," commented Mike Powell, Chairman of the Board of Checkmate, and General Partner, Sofinnova Ventures. "Art has successfully led the company to this critical stage in its growth, including this planned leadership transition. We are delighted to have Barry as CEO and Art as CSO. We are confident that they will successfully guide Checkmate to its next stage of evolution," continued Dr. Powell.

Mr. Barry Labinger brings to Checkmate nearly three decades of pharmaceutical and biotech industry experience, most recently serving as President, CEO, and Director of Biothera Pharmaceuticals, a clinical stage cancer immunotherapy company focused on innate immune activation. Prior to Biothera, he was Executive Vice President and President, Biosciences Division, at Emergent BioSolutions Inc., where he led the development and commercialization of oncology, immunology, and hematology products and product candidates. He previously held leadership roles at Human Genome Sciences, 3M Pharmaceuticals, and Immunex.

"I firmly believe in the importance of innate immune activation to enhance the benefits of other cancer immunotherapeutics," said Mr. Labinger. "CMP-001 has demonstrated best-in-class potential, and I’m excited to join Art, the Checkmate team, and our Board to maximize the potential of CMP-001 to improve outcomes for cancer patients."

"My initial goal in founding Checkmate was to determine if intratumoral TLR9 activation could induce tumor regression in anti-PD-1 refractory advanced cancer patients," Dr. Krieg commented. "Now that we have achieved that goal, I am delighted to turn over Checkmate’s leadership to Barry, so that I can focus my own efforts on the further scientific development of our platform. I believe that our complementary experience and our shared vision will enable us to accelerate and maximize Checkmate’s further development."

Proceeds from the financing will support ongoing clinical development of Checkmate’s lead product CMP-001 in advanced melanoma and non-small cell lung cancer (NSCLC) refractory to prior anti-PD-1 therapy, along with expansion into additional solid tumor types.

On December 12, 2018 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company focused on developing a pipeline of first-in-class AXL kinase inhibitors to treat multiple cancer indications, reported that the Company will be presenting key results from its Phase II clinical programme with selective AXL inhibitor bemcentinib at the DNB’s 9th Annual Nordic Healthcare Conference in Oslo, Norway, today at 10:15-10:40 CET (Press release, BerGenBio, DEC 12, 2018, View Source [SID1234532017]).

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The slides are available for download at the Company’s website: www.bergenbio.com/investors/presentations/

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "We have made significant progress during 2018 establishing clinical proof of concept for the remarkable utility of bemcentinib in cancers with high unmet clinical need and large market potential. We have shown that our once-a-day, oral selective AXL inhibitor is well tolerated as a monotherapy and in combination with immune-, targeted and chemotherapies. What is more, consistently we have seen that efficacy scales with AXL biomarker expression leading to superior response rates in AXL biomarker positive relapsed/refractory AML and MDS as a monotherapy as well as non-small cell lung cancer where we are combining with the immunotherapy blockbuster Keytruda. We have met all our operational milestones this year and are looking forward to starting a randomised phase II programme towards the end of H1 2019 based on key results obtained this year".

On December 12, 2018 Apexian Pharmaceuticals reported is shedding light on the question of how pre-leukemic cells transform into full-blown leukemia (Press release, Apexian Pharmaceuticals, DEC 12, 2018, View Source [SID1234532036]).

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Genetic mutations by themselves are rarely enough to flip the switch. Inflammation also plays a role. But, until now, the question of "how" remained unanswered.

Apexian Chief Science Officer Mark Kelley, PhD, and his colleagues presented their findings at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s December 1, 2018 meeting in San Diego, California. When a putative tumor-suppressor gene called TET2 does not function well, acute inflammation or infection can enhance the production of myeloid stem and progenitor cells in the bone marrow that are precursors to circulating mature myeloid cells. The TET2 loss of function amplifies; inflammatory proteins increase, and myeloid cells rapidly mature, increasing in sheer numbers as well as developing resistance to programmed cell death.

Myeloid cells, which contribute to immunity, are normally very short-lived. However, when those cells live too long or become too numerous, dangerous levels of inflammation can result. Using a mouse model, Kelley and his colleagues demonstrated that Apexian’s flagship compound APX3330 can prevent precancerous cells from proliferating and block cells from making inflammatory proteins.

Such anti-inflammatory therapy could be of clinical value in people carrying TET2 mutations.

"Apexian continues to develop a robust portfolio of APE1/Ref-1 compounds that have broad utility in oncology, hematology and other diseases," says Steve Carchedi, President and CEO. "We are excited by the recent scientific findings and continue to expand our research and development beyond solid tumors."

APX3330 also has clinical utility with solid tumors. A Phase 1 trial for patients with advanced solid tumors is concluding

On December 12, 2018 NETRIS Pharma, a clinical-stage company developing novel anticancer therapies targeting dependence receptors, reported successful completion of the first-in-human study on the effects of netrin-1 inhibition in patients with advanced solid tumors (Press release, Netris Pharma, DEC 12, 2018, View Source [SID1234532018]). The Phase 1 dose-escalation study showed that NP137, a first-in-class monoclonal anti-netrin-1 blocking antibody, was safe and well tolerated up to 20mg/kg, with no dose limiting toxicity (DLT), meeting the primary objective. In addition, patients with advanced uterine cancers exhibited encouraging signs of anti-tumor activity, including prolonged stable disease and objective response.

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"We are very pleased with the safety and tolerability profile of NP137 in this study, which enabled evaluation of netrin-1 inhibition in advanced solid tumors," said Philippe Cassier, MD, PhD, Head of Phase 1 unit at Centre Léon Bérard and Principal Investigator of the NP137 study.

"I am really impressed by the preliminary anti-tumor activity observed in this study with patients showing objective response and prolonged one-year disease control," added Professor Jean Yves Blay, MD, Ph.D. General Director of the Centre Léon Bérard and past president of EORTC.

The Phase 1 study was designed to evaluate the maximum tolerated dose, pharmacokinetics and pharmacodynamics, and establish the recommended dose for the Phase 1b/2 expansion study. NP137 was dosed every other week starting from 1 mg/kg up to 20mg/kg in heavily pre-treated patients with advanced solid tumors. Additional study objectives were to evaluate the adverse events (AE), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of NP137. The study enrolled a total of 19 patients in three French centers, the Centre Léon Bérard in Lyon, the Institut Claudius Régaud in Toulouse and the Institut de Cancérologie de l’Ouest in Nantes. A Phase 1 extension study with an additional 24 patients is ongoing to confirm the safety and tolerability of NP137, collect biopsies before and after treatment to allow measurement of potential biomarkers and confirm the preliminary clinical activity seen during dose escalation. The final phase 1a data will be submitted for presentation at an upcoming international medical conference.

"Meeting the primary objective of the dose-escalation part of this study and generating preliminary positive efficacy data, particularly in such chemotherapy-resistant patients, provide an important confirmation of our dependence receptor science and lay the groundwork for larger clinical studies with NP137 as a targeted approach to treat solid tumors in combination with chemotherapy, immune checkpoint inhibitors and tyrosine kinase inhibitors, » said Prof. Patrick Mehlen, Chief Executive Officer of NETRIS Pharma. « Additionally, we would like to thank the investigators, patients and caregivers for their participation in this study, and for contributing to our understanding of NP137 as we work to address a significant medical need. »

About NP137

Most types of tumors produce an abnormal amount of dependence receptors’ ligands, which prevents cells from dying. Netrin-1 is overexpressed in a large percentage of human cancers, including over two thirds of gynecologic cancers. Expression of netrin-1 often correlates with disease severity and no therapy has ever been tested against this new pathway.

NP137, a humanized monoclonal antibody of isotype IgG1 directed against netrin-1, is the first drug candidate developed by NETRIS Pharma. NP137 prevents the binding of netrin-1 on its dependence receptors, thereby re-inducing cancer cell death and impacting tumor cell plasticity. Pre-clinical studies show NP137 to have an anti-cancer effect as a monotherapy as well as synergistic effects in combination with chemotherapy, immune checkpoint inhibitors or tyrosine kinase inhibitors.