On October 3, 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 conduct its clinical trial to study Annamycin for the treatment of acute myeloid leukemia (AML) with the first of several hospitals desiring to be treatment centers (Press release, Moleculin, OCT 3, 2017, View Source [SID1234520760]).

“Now that our IND (investigational new drug) application is approved, the race is on to open treatment centers and begin recruiting patients,” commented Walter Klemp, Chairman and CEO of Moleculin. “We have identified 14 treatment sites that meet our criteria and have expressed an interest in participating, so there will be much more of this to come.”

“This first facility is a hematology clinic in a major hospital in Poland,” continued Mr. Klemp. “Because of the difference in process in Poland compared with the US, we were able to get this site signed up very shortly following the approval of our IND. We anticipate announcing additional sites over the coming months.”

Moleculin entered into this first agreement with a hospital in Poznan, Poland (Hospital of the Transfiguration of the Lord — Medical University in Poznan, Department of Hematology and Marrow Transplantation). The ability to treat patients in this and other Polish sites will require a separate regulatory approval in Poland based on the approved US IND. This is one of seven planned treatment sites in Poland.

On October 03, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, reported final clinical and translational research data from its OVATION Study, a Phase Ib dose escalating clinical trial combining GEN-1, the Company’s DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced Stage III/IV ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery (Press release, Celsion, OCT 3, 2017, View Source [SID1234520758]). GEN-1 is an IL-12 DNA plasmid vector formulated as a nanoparticle in a non-viral delivery system to cause the sustained local production and secretion of the Interleukin-12 (IL-12) protein loco-regionally to the tumor site.

The Company updated the translational data from the OVATION Study in a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Special Conference entitled “Addressing Critical Questions in Ovarian Cancer Research and Treatment” at the Wyndham Grand Pittsburgh Downtown in Pittsburgh, PA. The poster entitled “Immunological changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with neoadjuvant chemotherapy in newly diagnosed advanced ovarian cancer patients,” was presented by Dr. Khursheed Anwer, Celsion’s executive vice president and chief scientific officer in a poster session on Monday, October 2, 2017 from 6:00 PM to 8:30 PM.

The Company also held an Advisory Board Meeting on September 27, 2017 with the clinical investigators and scientific experts including those from Roswell Park Cancer Institute, Vanderbilt University Medical School, and M.D. Anderson Cancer Center to review and finalize clinical, translational research and safety data from the OVATION Study in order to determine the next steps forward for this exciting new immunotherapy. With the endorsement and recommendations from the Advisory Board, the Company expects to file a next phase protocol with FDA later this year.

Translational Research Data

Key translational research findings from all evaluable patients are consistent with the earlier reports from partial analysis of the data and are summarized below:

The intraperitoneal treatment of GEN-1 in conjunction with neoadjuvant chemotherapy resulted in dose dependent increases in IL-12 and Interferon-gamma (IFN-g) levels that were predominantly in the peritoneal fluid compartment with little to no changes observed in the patients’ systemic circulation. These and other post-treatment changes including decreases in VEGF levels in peritoneal fluid are consistent with an IL-12 based immune mechanism.

Consistent with the previous partial reports, the effects observed in the IHC analysis were pronounced decreases in the density of immunosuppressive T-cell signals (Foxp3, PD-1, PDL-1, IDO-1) and increases in CD8+ cells in the tumor microenvironment.

The ratio of CD8+ cells to immunosuppressive cells was increased in approximately 75% of patients suggesting an overall shift in the tumor microenvironment from immunosuppressive to pro-immune stimulatory following treatment with GEN-1. An increase in CD8+ to immunosuppressive T-cell populations is a leading indicator and believed to be a good predictor of improved overall survival.

Analysis of peritoneal fluid by cell sorting, not reported before, shows treatment-related decrease in the percentage of immunosuppressive T-cell (Foxp3+), which is consistent with the reduction of Foxp3+ T-cells in the primary tumor tissue, and a shift in tumor naïve CD8+ cell population to more efficient tumor killing memory effector CD8+ cells.

These translational research findings demonstrate that GEN-1 in ovarian cancer patients is biologically active and creates a shift in the primary tumor and in the surrounding tumor environment in the peritoneal cavity that promotes a pro-immune T-cell population dynamic and conversion of tumor naïve T-cell into cytotoxic effector T-cells in the tumor microenvironment.

“These distinct immunological changes in the local disease environment are likely to translate into clinical benefit and warrant the continued development of our GEN-1 IL-12 immunotherapy as a potential adjuvant, in both first and second-line ovarian cancer,” said Dr. Kunle Odunsi, Deputy Director, Chair of Gynecologic Oncology and Center for Immunotherapy Executive Director at Roswell Park Cancer Institute. “Furthermore, pro-immune changes in the tumor microenvironment appear to support research combining GEN-1 with other exciting immuno-oncology therapies including adaptive T-cell and check point inhibitors.”

Clinical Data

Celsion also reported highly encouraging clinical data from the first fourteen patients who have completed treatment in the OVATION Study. GEN-1 plus standard chemotherapy produced positive clinical results, with no dose limiting toxicities and promising dose dependent efficacy signals which correlate well with successful surgical outcomes as summarized below:

Of the fourteen patients treated in the entire study, two (2) patients demonstrated a complete response, ten (10) patients demonstrated a partial response and two (2) patients demonstrated stable disease, as measured by RECIST criteria. This translates to a 100% disease control rate (“DCR”) and an 86% objective response rate (“ORR”). Of the five patients treated in the highest dose cohort, there was a 100% objective response rate with one (1) complete response and four (4) partial responses.

Fourteen patients had successful resections of their tumors, with nine (9) patients (64%) having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. Seven out of eight (87%) patients in the highest two dose cohorts experienced a R0 surgical resection. All five patients treated at the highest dose cohort experienced a R0 surgical resection.

All patients experienced a clinically significant decrease in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells.

Of the eight patients who have received GEN-1 treatment over one year ago (cohort 1 – 3) and are being followed; only two patients’ cancer has progressed. This compares favorably to the historical median progression free survival (PFS) of 12 months for newly-diagnosed patients with Stage III and IV ovarian cancer that undergo neoadjuvant chemotherapy followed by interval debulking surgery. Of the remaining six patients who have been on the study for over one year, their average PFS as of September 30, 2017 is 18 months with the longest progression-free patient at 24 months.

“We have completed enrollment of our Phase Ib OVATION Study in newly diagnosed ovarian cancer patients to determine GEN-1’s clinical and biological activity in combination with standard chemotherapy. The remarkable surgical outcomes for all patients completing the prescribed eight weekly treatments of GEN-1 reinforce our belief in the promise of GEN-1’s ability to work safely and effectively in advanced ovarian cancer,” said Dr. Nicholas Borys, Celsion’s senior vice president and chief medical officer. “The Advisory Board Meetings held in late September 2017 with our clinical investigators and scientific experts in immuno-oncology provided an important endorsement of our development program for this innovative immunotherapy for first line ovarian cancer.”

The poster presentation will be available on Celsion’s website under “News & Investors – Scientific Presentations.”

OVATION Study Design

The Phase Ib trial was designed to evaluate weekly intraperitoneal dosing of GEN-1 in combination with neoadjuvant chemotherapy, the standard of care for patients newly diagnosed with ovarian cancer. Concurrently with neoadjuvant chemotherapy, enrolled patients will receive escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, with interval debulking surgery to follow. The regimen will primarily be evaluated for its safety and tolerability.

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer.

On October 03, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, reported final clinical and translational research data from its OVATION Study, a Phase Ib dose escalating clinical trial combining GEN-1, the Company’s DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced Stage III/IV ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery (Press release, Celsion, OCT 3, 2017, View Source [SID1234520758]). GEN-1 is an IL-12 DNA plasmid vector formulated as a nanoparticle in a non-viral delivery system to cause the sustained local production and secretion of the Interleukin-12 (IL-12) protein loco-regionally to the tumor site.

The Company updated the translational data from the OVATION Study in a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Special Conference entitled “Addressing Critical Questions in Ovarian Cancer Research and Treatment” at the Wyndham Grand Pittsburgh Downtown in Pittsburgh, PA. The poster entitled “Immunological changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with neoadjuvant chemotherapy in newly diagnosed advanced ovarian cancer patients,” was presented by Dr. Khursheed Anwer, Celsion’s executive vice president and chief scientific officer in a poster session on Monday, October 2, 2017 from 6:00 PM to 8:30 PM.

The Company also held an Advisory Board Meeting on September 27, 2017 with the clinical investigators and scientific experts including those from Roswell Park Cancer Institute, Vanderbilt University Medical School, and M.D. Anderson Cancer Center to review and finalize clinical, translational research and safety data from the OVATION Study in order to determine the next steps forward for this exciting new immunotherapy. With the endorsement and recommendations from the Advisory Board, the Company expects to file a next phase protocol with FDA later this year.

Translational Research Data

Key translational research findings from all evaluable patients are consistent with the earlier reports from partial analysis of the data and are summarized below:

The intraperitoneal treatment of GEN-1 in conjunction with neoadjuvant chemotherapy resulted in dose dependent increases in IL-12 and Interferon-gamma (IFN-g) levels that were predominantly in the peritoneal fluid compartment with little to no changes observed in the patients’ systemic circulation. These and other post-treatment changes including decreases in VEGF levels in peritoneal fluid are consistent with an IL-12 based immune mechanism.

Consistent with the previous partial reports, the effects observed in the IHC analysis were pronounced decreases in the density of immunosuppressive T-cell signals (Foxp3, PD-1, PDL-1, IDO-1) and increases in CD8+ cells in the tumor microenvironment.

The ratio of CD8+ cells to immunosuppressive cells was increased in approximately 75% of patients suggesting an overall shift in the tumor microenvironment from immunosuppressive to pro-immune stimulatory following treatment with GEN-1. An increase in CD8+ to immunosuppressive T-cell populations is a leading indicator and believed to be a good predictor of improved overall survival.

Analysis of peritoneal fluid by cell sorting, not reported before, shows treatment-related decrease in the percentage of immunosuppressive T-cell (Foxp3+), which is consistent with the reduction of Foxp3+ T-cells in the primary tumor tissue, and a shift in tumor naïve CD8+ cell population to more efficient tumor killing memory effector CD8+ cells.

These translational research findings demonstrate that GEN-1 in ovarian cancer patients is biologically active and creates a shift in the primary tumor and in the surrounding tumor environment in the peritoneal cavity that promotes a pro-immune T-cell population dynamic and conversion of tumor naïve T-cell into cytotoxic effector T-cells in the tumor microenvironment.

“These distinct immunological changes in the local disease environment are likely to translate into clinical benefit and warrant the continued development of our GEN-1 IL-12 immunotherapy as a potential adjuvant, in both first and second-line ovarian cancer,” said Dr. Kunle Odunsi, Deputy Director, Chair of Gynecologic Oncology and Center for Immunotherapy Executive Director at Roswell Park Cancer Institute. “Furthermore, pro-immune changes in the tumor microenvironment appear to support research combining GEN-1 with other exciting immuno-oncology therapies including adaptive T-cell and check point inhibitors.”

Clinical Data

Celsion also reported highly encouraging clinical data from the first fourteen patients who have completed treatment in the OVATION Study. GEN-1 plus standard chemotherapy produced positive clinical results, with no dose limiting toxicities and promising dose dependent efficacy signals which correlate well with successful surgical outcomes as summarized below:

Of the fourteen patients treated in the entire study, two (2) patients demonstrated a complete response, ten (10) patients demonstrated a partial response and two (2) patients demonstrated stable disease, as measured by RECIST criteria. This translates to a 100% disease control rate (“DCR”) and an 86% objective response rate (“ORR”). Of the five patients treated in the highest dose cohort, there was a 100% objective response rate with one (1) complete response and four (4) partial responses.

Fourteen patients had successful resections of their tumors, with nine (9) patients (64%) having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. Seven out of eight (87%) patients in the highest two dose cohorts experienced a R0 surgical resection. All five patients treated at the highest dose cohort experienced a R0 surgical resection.

All patients experienced a clinically significant decrease in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells.

Of the eight patients who have received GEN-1 treatment over one year ago (cohort 1 – 3) and are being followed; only two patients’ cancer has progressed. This compares favorably to the historical median progression free survival (PFS) of 12 months for newly-diagnosed patients with Stage III and IV ovarian cancer that undergo neoadjuvant chemotherapy followed by interval debulking surgery. Of the remaining six patients who have been on the study for over one year, their average PFS as of September 30, 2017 is 18 months with the longest progression-free patient at 24 months.

“We have completed enrollment of our Phase Ib OVATION Study in newly diagnosed ovarian cancer patients to determine GEN-1’s clinical and biological activity in combination with standard chemotherapy. The remarkable surgical outcomes for all patients completing the prescribed eight weekly treatments of GEN-1 reinforce our belief in the promise of GEN-1’s ability to work safely and effectively in advanced ovarian cancer,” said Dr. Nicholas Borys, Celsion’s senior vice president and chief medical officer. “The Advisory Board Meetings held in late September 2017 with our clinical investigators and scientific experts in immuno-oncology provided an important endorsement of our development program for this innovative immunotherapy for first line ovarian cancer.”

The poster presentation will be available on Celsion’s website under “News & Investors – Scientific Presentations.”

OVATION Study Design

The Phase Ib trial was designed to evaluate weekly intraperitoneal dosing of GEN-1 in combination with neoadjuvant chemotherapy, the standard of care for patients newly diagnosed with ovarian cancer. Concurrently with neoadjuvant chemotherapy, enrolled patients will receive escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, with interval debulking surgery to follow. The regimen will primarily be evaluated for its safety and tolerability.

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer.

On October 3, 2017 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported that Margo Heath-Chiozzi, M.D., has joined the Company as Senior Vice President, Regulatory Affairs (Press release, Celldex Therapeutics, OCT 3, 2017, View Source [SID1234520756]). She was previously Vice President, Global Submissions and Regulatory Policy at Bristol-Myers Squibb Company, where she provided executive global regulatory strategy leading to nine product approvals. Dr. Heath-Chiozzi brings over 25 years of experience in senior leadership roles in regulatory sciences, pharmacogenetics and product development within the pharmaceutical industry and as a practicing physician and clinical researcher.

“Dr. Heath-Chiozzi’s strong track record of drug approvals and her exceptional understanding of the regulatory environment position her well to lead our global regulatory strategy,” said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. “She is sincerely passionate about drug development and making a difference in the lives of patients, and we look forward to working with her as we execute across our deep pipeline of drug candidates.”

“I’m looking forward to working with the Celldex team to develop commercial strategies across its deep pipeline, especially as topline results from the METRIC study of glembatumumab vedotin in patients with triple-negative breast cancer are anticipated within the coming months,” said Dr. Heath-Chiozzi. “It’s an exciting time for the organization, and I’m thrilled to be a member of the team.”

Dr. Heath-Chiozzi joined Bristol-Myers Squibb in 2003, and prior to her most recent role, she served as Vice President, Global Regulatory Strategy, contributing to several business units including oncology, immunology, virology and genetically defined diseases. While at Bristol-Myers Squibb, she supported the global launches of several successful therapies in the areas of oncology, inflammation and infectious disease, including Yervoy, Erbitux, Orencia, Sprycel, Daklinza, Sunvepra, Baraclude, Atripla and Reyataz. From 1995 to 2003, Dr. Heath-Chiozzi served in roles of increasing responsibility at Abbott Laboratories, including Medical Director, Pharmacogenetics; Senior Director, Global Marketed Product Development and Outcomes Research; and Global Project Head, Abbott/Millennium Obesity/Diabetes Alliance. Before joining Abbott, she was appointed to the University of Hawaii John A. Burns School of Medicine, where she served as Assistant Professor, and was concurrently Director of the HIV Research Clinical at the Queen’s Medical Center as well as Director of the Women’s Immunology Clinical at the Kapiolani Medical Center for Women and Children, in Honolulu. Dr. Heath-Chiozzi received her B.S. and M.D. from the University of Utah. She received further medical training in internal medicine at Duke University and completed fellowships in infectious disease at Brigham & Women’s Hospital and Dana-Farber Cancer Institute in Boston.

On October 3, 2017 Roche (SIX: RO, ROG; OTCQX:RHHBY), reported the launch of the NAVIFY Tumor Board solution, a clinical workflow and decision support software that optimises decision-making for cancer patient case reviews in tumor boards, or multi-disciplinary team meetings (Press release, Hoffmann-La Roche, OCT 3, 2017, View Source [SID1234520752]). The solution fundamentally changes the way these meetings are organised and conducted. It is initially available in the US, UK, Germany, Spain, Sweden, and Switzerland.

Tumor board coordination is labour intensive and time consuming for health care providers with patients’ medical history, biomarkers, tumor information, radiology images, microscope slide images, pathology reports, and electronic medical record notes frequently having to be collected and organised manually.

The new NAVIFY Tumor Board solution streamlines and standardizes workflows by aggregating relevant patient data from these disparate sources into a workflow software solution that facilitates efficient team collaboration, reduces errors, and gives the care team more time to evaluate potential treatment options.
To facilitate interaction, the NAVIFY Tumor Board solution also allows remote participation of experts from outside the location during the meeting.

“Oncology care teams are now able to collaborate on the review of patient cases and tailor treatments to the individual with a higher degree of confidence and more efficiently,” said Roland Diggelmann, Chief Executive Officer, Roche Diagnostics. “At Roche, we are passionate about personalised healthcare and providing decision support that helps ensure that all available data is used to accelerate and optimise patient care.”

About NAVIFY

Roche Diagnostics is launching the NAVIFY brand demonstrating its commitment to provide healthcare professionals with digital decision support solutions that transform patient care. The NAVIFY portfolio’s first product is the NAVIFY Tumor Board solution, being launched. The portfolio will in the near future, evolve rapidly to include additional decision support applications and workflow products that address challenges faced by healthcare providers as well as research and development applications.

Patient data security and privacy are of the highest priority for Roche. The NAVIFY Tumor Board solution is built on a secure cloud platform that is HIPAA compliant.