On November 5, 2019 Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported positive interim results from Inovio’s Phase 2 study (NCT03491683) of newly diagnosed glioblastoma multiforme (GBM) combining Inovio’s INO-5401, a T cell-activating immunotherapy encoding for three tumor-associated antigens (hTERT, WT1, and PSMA), and INO-9012, an immune activator encoding IL-12, in combination with Libtayo (cemiplimab), a PD-1 blocking antibody developed by Regeneron Pharmaceuticals (NASDAQ: REGN) in collaboration with Sanofi (Press release, Inovio, NOV 5, 2019, View Source [SID1234550328]). The data will be featured in a late-breaking poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2019 Annual Meeting in National Harbor, Maryland, November 6-10.

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Key interim data from the 52-patient clinical trial showed that 80% (16 of 20) of MGMT gene promoter methylated patients and 75% (24 of 32) of unmethylated patients were progression-free at six months (PFS6) measured from the time of their first dose, substantially exceeding historical standard-of-care data.

This immunotherapy combination with a PD-1 checkpoint inhibitor also exhibited supportive safety, tolerability, and immunogenicity data and suggested an acceptable safety profile consistent with that of Libtayo and Inovio’s platform technology. The majority of patients tested had a T cell immune response to one or more tumor-associated antigens encoded by INO-5401. Immune responses to all three tumor-associated antigens were demonstrated in this study. Inovio plans to report 12- and 18-month overall survival data next year.

Dr. David Reardon, M.D., Coordinating Principal Investigator of the study and the Clinical Director for Neuro-Oncology at the Dana-Farber Cancer Institute, said, "This innovative trial provides promising information that the combination of INO-5401 plus INO-9012, a T cell-promoting therapy, combined with Libtayo, a checkpoint inhibitor, may provide clinically meaningful benefit in this very difficult to treat disease."

Dr. J. Joseph Kim, Inovio’s President & CEO, said, "Our new data demonstrates the potential of our immunotherapies utilizing tumor-associated antigens in cancer treatments. Our goal in this GBM trial is to increase progression-free and overall survival of patients facing a disease where neither the standard of care nor clinical outcomes have significantly advanced in decades. Previously, other checkpoint inhibitor treatment alone in GBM trials did not show any meaningful clinical benefit over standard of care. However, the addition of INO-5401 and its ability to generate antigen-specific T cells demonstrated early efficacy signals in progression-free survival. We look forward to reporting additional data including overall survival at months 12 and 18 from the trial in the coming year."

Poster Details

Poster 858:

An Open-Label, Multi-center Trial of INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination with Cemiplimab in Subjects with Newly-Diagnosed Glioblastoma (GBM)

Category:

Late-Breaker

Date/Time:

Friday, Nov. 8th, 12:30 – 2 p.m. and Saturday, Nov. 9th 12:35 – 2:05 p.m.

Location:

Displayed in the Potomac Foyer (outside the Plenary session room, Potomac Ballroom)

Study Design

The trial was designed to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with Libtayo, with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM). This is a Phase 1/2, open-label, multi-center trial conducted in 52 evaluable patients with GBM. There were 2 cohorts in this trial. Cohort A were participants with a tumor with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Cohort B included participants with a tumor with a MGMT methylated promoter or who have indeterminate MGMT status. Both cohorts received INO-5401 and INO-9012 and Libtayo at the same doses and on the same dosing schedule, and both cohorts received radiation and temozolomide (TMZ), if clinically indicated. Interim data presented here and at SITC (Free SITC Whitepaper) was obtained as of October 2019 and final study data is expected in Q4 2020. For more information of the clinical study, see www.clinicaltrials.gov, identifier NCT03491683.

About Glioblastoma Multiforme (GBM)

GBM is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, despite a limited number of new therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the median progression-free survival is approximately 7 months. In the U.S., the estimated annual incidence of GBM is 11,362 cases or 3.21 cases per 100,000 persons and the median age at diagnosis is 65 years.

About INO-5401 and INO-9012

INO-5401 encodes for Inovio’s SynCon antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens were reported to be over-expressed, and often mutated, in a variety of human cancers, and targeting these antigens may prove efficacious in the treatment of patients with cancer. INO-9012 encodes for IL-12, which is a T cell immune activator.

On November 5, 2019 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that it will host a live conference call and webcast at 8:30 a.m. ET on Tuesday, November 12, 2019 to report its third quarter 2019 financial results and provide a corporate update (Press release, Syros Pharmaceuticals, NOV 5, 2019, View Source [SID1234550344]).

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To access the live conference call, please dial 866-595-4538 (domestic) or 636-812-6496 (international), and refer to conference ID 1994858. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the presentation.

On November 5, 2019 Seres Therapeutics, Inc. (Nasdaq: MCRB) reported financial results for the three months ended September 30, 2019 and provided a business update (Press release, Seres Therapeutics, NOV 5, 2019, View Source [SID1234550360]).

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"Seres continues to advance our microbiome programs, and the Company is well resourced to reach important corporate milestones in 2020, including two late-stage clinical readouts: SER-287 Phase 2b study in mild-to-moderate ulcerative colitis and SER-109 Phase 3 study in recurrent C. difficile infection," said Eric D. Shaff, President and Chief Executive Officer at Seres. "We are very pleased that our SER-109 ECOSPOR III study is now approaching target enrollment. SER-109 could provide patients with a meaningful new treatment option and also provide definitive clinical validation for our microbiome therapeutic approach. We are eagerly looking forward to top-line results from both of these important programs."

Program Updates and Corporate Highlights

SER-287 Phase 2b ECO-RESET study in ulcerative colitis: SER-287 is an orally-administered, biologically-derived, live microbiome therapeutic candidate designed to modulate the gastrointestinal microbiome of individuals with ulcerative colitis. Seres continues to enroll the SER-287 Phase 2b ECO-RESET induction study in patients with active mild-to-moderate ulcerative colitis. The SER-287 Phase 2b ECO-RESET study is expected to enroll approximately 201 patients. Based on U.S. Food and Drug Administration feedback, Seres expects that with positive Phase 2b study results, the study could serve as one of two pivotal trials to enable a SER-287 Biologics License Application submission. Seres expects Phase 2b ECO-RESET study top-line results in the second half of 2020.
SER-109 Phase 3 ECOSPOR III study in recurrent C. difficile infection: SER-109 is an orally-administered, biologically-derived, live microbiome therapeutic candidate designed to restore the depleted, or dysbiotic, gastrointestinal microbiome of patients with recurrent C. difficile infection. The Company continues to enroll the ECOSPOR III trial, which is evaluating efficacy and safety in 188 patients with recurrent C. difficile infection. All patients enrolled in ECOSPOR III are required to test positive for C. difficile cytotoxin to ensure enrollment of only patients with an active C. difficile infection. As of October 31, ECOSPOR III was more than 85% enrolled, and top-line study results are expected in mid-2020.
SER-301 preclinical candidate for ulcerative colitis: The Company has nominated the lead candidate for SER-301, a rationally-designed, live microbiome therapeutic for ulcerative colitis. Next-generation, rationally-designed microbiome therapeutics may provide important benefits that include the optimization of pharmacological properties for target diseases and streamlined manufacturing. The consortia of bacteria in SER-301 are designed to modify the microbiome and microbe-associated metabolites in the gastrointestinal tract to modulate ulcerative colitis-relevant anti-inflammatory and immune pathways and to improve epithelial barrier integrity. SER-301 incorporates species associated with clinical efficacy in prior Seres human studies. Further, bacterial species selected for inclusion in SER-301 have been confirmed to engraft across human subjects. The consortia has demonstrated the capacity to modulate disease-relevant cellular mechanisms in human cell-based screening assays and in vivo models. Seres is entitled to a $10 million milestone payment associated with the SER-301 Phase 1 clinical study from its ongoing collaboration with Nestlé Health Science. Seres expects to initiate clinical development in early 2020.
SER-401 Phase 1b in metastatic melanoma: SER-401 is an orally-administered, biologically-derived, live microbiome therapeutic candidate comprising bacteria that reflect the bacterial signature in the gastrointestinal microbiome associated with response to checkpoint inhibitor immunotherapy. The ongoing Phase 1b study, supported by the Parker Institute for Cancer Immunotherapy and The University of Texas MD Anderson Cancer Center, will evaluate the potential for SER-401 to improve clinical response to nivolumab, an approved anti-PD-1 checkpoint inhibitor therapy, and will evaluate tumor biopsies and various biomarkers. Seres expects to obtain SER-401 Phase 1b preliminary study results in the second half of 2020.
New debt financing: Seres entered into a debt financing agreement with Hercules Capital in October 2019 that provides the Company with up to $50 million in additional capital. The Company received a first tranche of approximately $25 million following the agreement closing. Two subsequent tranches of $12.5 million each would become available to the Company upon the achievement of certain milestones.
Financial Results
Seres reported a net loss of $16.4 million for the third quarter of 2019, as compared to a net loss of $21.9 million for the same period in 2018. The third quarter net loss was driven primarily by clinical and development expenses, personnel expenses and ongoing development of the Company’s microbiome therapeutics platform. The third quarter net loss figure was inclusive of $7.0 million in recognized revenue associated primarily with the Company’s collaborations with Nestlé Health Science and AstraZeneca.

Research and development expenses for the third quarter of 2019 were $18.3 million, as compared to $23.7 million for the same period in 2018. The research and development expense was primarily related to Seres’ late stage SER-109 and SER-287 clinical development programs.

General and administrative expenses for the third quarter of 2019 were $5.9 million, as compared to $7.6 million for the same period in 2018. General and administrative expenses were primarily due to headcount, professional fees and facility costs.

Seres ended the third quarter with approximately $83.8 million in cash, cash equivalents and investments. This amount does not include the $25 million in debt capital obtained in October 2019.

Cash resources are expected to fund operating expenses and capital expenditure requirements, excluding net cash flows from future business development activities or potential incoming milestone payments, into the second quarter of 2021.

Conference Call Information
Seres’ management will host a conference call today, Nov. 5, 2019 at 8:30 a.m. ET. To access the conference call, please dial 844-277-9450 (domestic) or 336-525-7139 (international) and reference the conference ID number 3577505. To join the live webcast, please visit the "Investors and Media" section of the Seres website at www.serestherapeutics.com.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.

On November 5, 2019 BD (Becton, Dickinson and Company) (NYSE: BDX), a leading global medical technology company, reported quarterly revenues of $4.584 billion for the fourth fiscal quarter ended September 30, 2019 (Press release, BD Pharmaceutical Systems, NOV 5, 2019, View Source [SID1234550376]). This represents an increase of 4.1 percent over the prior-year period. On a comparable, currency-neutral basis, revenues increased 6.2 percent over the prior-year period.

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For the full fiscal year ended September 30, 2019, revenues of $17.290 billion increased 8.2 percent from the prior-year period. On a comparable, currency-neutral basis, full fiscal year revenues of $17.281 billion grew 5.1 percent.

"We are very proud of our accomplishments in fiscal year 2019. Our performance this year demonstrates our ability to overcome multiple headwinds and deliver on our financial and operational goals," said Vincent A. Forlenza, chairman and CEO. "We enter fiscal 2020 with continued optimism. There are significant opportunities ahead to leverage the capabilities we’ve built to better serve our customers and their patients around the world. It has been a privilege to lead BD and our global team of talented associates. I’m confident that under Tom Polen’s leadership the company will further accelerate its impact as BD enters its next phase of value creation."

Fourth Quarter and Twelve-Month Fiscal 2019 Operating Results
As reported, diluted earnings per share for the fourth quarter were $0.41, compared with $(0.64) in the prior-year period. This represents an increase of 164.1 percent. Adjusted diluted earnings per share were $3.31, compared with $2.93 in the prior-year period. This represents an increase in adjusted diluted earnings per share of 13.0 percent, or 12.3 percent on a currency-neutral basis.

For the twelve-month period ended September 30, 2019, as reported, diluted earnings per share were $3.89, compared with $0.60 in the prior-year period. This represents an increase of 548.3 percent. Adjusted diluted earnings per share were $11.68, compared with $11.01 in the prior-year period. This represents an increase in adjusted diluted earnings per share of 6.1 percent, or 11.9 percent on a currency-neutral basis.

Segment Results
In the BD Medical segment, as reported, worldwide revenues for the quarter of $2.437 billion increased 3.9 percent over the prior-year period, or 5.3 percent on a currency-neutral basis. The segment’s results were driven by performance in the Medication Management Solutions and Pharmaceutical Systems units.

For the twelve-month period ended September 30, 2019, BD Medical revenues were $9.064 billion as reported, which represents an increase of 5.2 percent over the prior-year period. On a comparable, currency-neutral basis, BD Medical revenues increased 5.1 percent.

In the BD Life Sciences segment, as reported, worldwide revenues for the quarter of $1.134 billion increased 2.3 percent over the prior-year period. On a comparable, currency-neutral basis, revenues increased 6.9 percent. Revenue growth was driven by performance in the Diagnostic Systems and Biosciences units.

For the twelve-month period ended September 30, 2019, BD Life Sciences revenues were $4.300 billion as reported, which represents a decrease of 0.7 percent from the prior-year period. On a comparable, currency-neutral basis, BD Life Sciences revenues of $4.291 billion increased 4.9 percent.

In the BD Interventional segment, as reported, worldwide revenues for the quarter of $1.013 billion increased 6.9 percent over the prior-year period, or 7.7 percent on a currency-neutral basis. The segment’s results were driven by performance in the Surgery and Urology and Critical Care units.

For the twelve-month period ended September 30, 2019, BD Interventional revenues were $3.926 billion as reported, which represents an increase of 29.3 percent over the prior-year period. On a comparable, currency-neutral basis, BD Interventional revenues increased 5.5 percent.

Geographic Results
As reported, fourth quarter revenues in the U.S. of $2.562 billion increased 4.6 percent over the prior-year period. On a comparable basis, U.S. revenues increased 4.9 percent over the prior-year period. Growth in the U.S. was driven by the Medication Management Solutions unit within the BD Medical segment, the Biosciences unit within the BD Life Sciences segment, and the Surgery and Urology and Critical Care units with the BD Interventional segment.

As reported, revenues outside of the U.S. of $2.022 billion increased 3.5 percent over the prior-year period. On a comparable, currency-neutral basis, revenues outside of the U.S. increased 7.9 percent over the prior-year period. International revenue growth was driven by performance in Europe, Asia Pacific and EMA.

For the twelve-month period ended September 30, 2019, U.S. revenues were $9.730 billion as reported, which represents an increase of 11.0 percent over the prior-year period. On a comparable basis, U.S. revenues of $9.726 billion increased 4.5 percent over the prior-year period. As reported, revenues outside of the U.S. of $7.560 billion increased 4.8 percent over the prior-year period. On a comparable, currency-neutral basis, revenues outside the U.S. of $7.555 billion increased 5.9 percent over the prior-year period.

Fiscal 2020 Outlook for Full Year
The company expects full fiscal year 2020 revenues to increase 4.0 to 4.5 percent as reported, or 5.0 to 5.5 percent on a currency-neutral basis.

The company expects full fiscal year 2020 adjusted diluted earnings per share to be between $12.50 and $12.65. This represents growth of approximately 9.5 to 11.0 percent on a currency-neutral basis over fiscal 2019 adjusted diluted earnings per share of $11.68, or growth of approximately 7.0 to 8.5 percent including the estimated unfavorable impact of foreign currency. Adjusted diluted earnings per share guidance includes an adverse impact of approximately 500 basis points related to the expiration of the Gore royalty.

Adjusted diluted earnings per share for fiscal 2020 excludes potential charges or gains that may be recorded during the fiscal year, such as, among other things, the non-cash amortization of intangible assets, acquisition-related charges, and certain tax matters. BD does not attempt to provide reconciliations of forward-looking non-GAAP earnings guidance to the comparable GAAP measure because the impact and timing of these potential charges or gains is inherently uncertain and difficult to predict and is unavailable without unreasonable efforts. In addition, the company believes such reconciliations would imply a degree of precision and certainty that could be confusing to investors. Such items could have a substantial impact on GAAP measures of BD’s financial performance.

Conference Call Information
A conference call regarding BD’s fourth quarter results will be broadcast live on BD’s website, www.bd.com/investors, along with related slides, at 8:00 a.m. (ET) Tuesday, November 5, 2019. The conference call will be available for replay on BD’s website, www.bd.com/investors, or at 1-800-585-8367 (domestic) and 1-404-537-3406 (international) through the close of business on Tuesday, November 12, 2019, confirmation number 5994332.

On November 5, 2019 The University of Texas MD Anderson Cancer Center and Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported an exclusive license agreement and research agreement to develop cord blood-derived chimeric antigen receptor-directed natural killer (CAR NK)-cell therapies, ‘armored’ with IL-15, for the treatment of B-cell malignancies and other cancers (Press release, Takeda, NOV 5, 2019, View Source [SID1234550313]).

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Under the agreement, Takeda will receive access to MD Anderson’s CAR NK platform and the exclusive rights to develop and commercialize up to four programs, including a CD19-targeted CAR NK-cell therapy and a B-cell maturation antigen (BCMA)-targeted CAR NK-cell therapy. Takeda and MD Anderson will also conduct a research collaboration to further develop these CAR NK programs.

"Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient setting—enabling more patients to be treated effectively, quickly and with minimal toxicities," said Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson. "With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments."

A Novel Approach to Delivering Off-the-Shelf CARs in an Outpatient Setting
MD Anderson’s allogeneic CAR NK platform isolates NK cells from umbilical cord blood and engineers them to express CARs against specified cancer targets. CAR NK cells are modified with a retroviral vector to deliver genes and enhance their effectiveness to attack specific tumors. A CD19 CAR increases the cells’ specificity for B-cell malignancies while the immunocytokine IL-15 enhances the proliferation and survival of the CAR NK cells in the body.

In contrast to current CAR T-cell therapies that utilize a patient’s own genetically modified T-cells and require a multi-week manufacturing process, CAR NK cells are intended to be manufactured from a non-related donor source and stored for off-the-shelf use, allowing treatment to be delivered more rapidly.

It is anticipated that the CD19 CAR NK-cell therapy could be administered in an outpatient setting. In an ongoing phase 1/2a clinical study treating patients with relapsed and refractory B-cell malignances, the CD19 CAR NK-cell therapy has not been associated with the severe cytokine release syndrome (CRS) or neurotoxicity observed with existing CAR-T therapies.

The development of MD Anderson’s CAR NK platform is led by Dr. Rezvani and is further supported by the adoptive cell therapy platform, Chronic Lymphocytic Leukemia Moon Shot and B-Cell Lymphoma Moon Shot, all part of the institution’s Moon Shots Program, a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients’ lives.

Takeda: Accelerating the Development of Multiple Next-Generation CAR Platforms
"MD Anderson’s CAR NK platform represents the curative potential of cell therapies, which is why we are establishing the CD19 CAR NK as our lead cell therapy candidate in oncology," said Andy Plump, M.D., Ph.D., President of Research and Development at Takeda. "We need to work swiftly and with purpose, and as such, we intend to initiate a pivotal study of the CD19 CAR NK in 2021."

In addition to CAR NK-cell therapies, Takeda and its partners are investigating multiple approaches to improving the safety, efficacy and accessibility of first-generation CAR T-cell therapies including gamma delta CAR Ts, induced pluripotent stem cell-derived CAR Ts, CAR Ts targeting solid tumors, and other next-generation approaches. Takeda plans to advance five oncology cell therapies to the clinic by the end of FY20.1 These platforms are being developed both with partners and by applying the expertise of Takeda’s translational cell therapy engine which provides bioengineering, chemistry, manufacturing and control (CMC), clinical and translational capabilities in a single footprint to overcome many of the manufacturing challenges experienced in cell therapy development.

Takeda is responsible for the development, manufacturing and commercialization of CAR NK products resulting under the agreement. MD Anderson will receive an upfront payment and is eligible to receive development and commercial milestones for each target as well as tiered royalties on net sales of any such CAR NK product.

MD Anderson and Takeda will continue research for the additional targets and CAR NK platform under the direction of a joint research committee. MD Anderson will implement an Institutional Conflict of Interest Management and Monitoring Plan for this research.