On October 24, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX) reported that final long-term results from the Phase 3 GENUINE study demonstrated that ublituximab in combination with ibrutinib improved progression-free survival (PFS), as determined by Independent Review Committee (IRC) (Press release, TG Therapeutics, OCT 24, 2019, View Source [SID1234542482]). The GENUINE Phase 3 study evaluated ublituximab, the Company’s novel, glycoengineered anti-CD20 monoclonal antibody, in combination with ibrutinib, compared to ibrutinib monotherapy in patients with relapsed/refractory high-risk chronic lymphocytic leukemia (CLL). As previously reported, the GENUINE study met its primary endpoint of improved IRC-assessed overall response rate (ORR), as well as increased centrally-assessed rate of minimal residual disease (MRD). The combination of ublituximab and ibrutinib was well tolerated with no new safety signals identified at a median follow-up of >4 years.

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The Company plans to present these final data at a future medical conference, as well as share the results with the U.S. Food and Drug Administration (FDA).

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "We are pleased with the final results from the Phase 3 GENUINE trial with median follow-up of over 4 years. The improvement in PFS observed in these high-risk CLL patients is extremely encouraging, and we look forward to presenting the full data at a future medical conference."

ABOUT THE PHASE 3 GENUINE STUDY

The Phase 3 GENUINE study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of ublituximab in combination with ibrutinib compared to ibrutinib monotherapy in adult patients with high-risk chronic lymphocytic leukemia (CLL) who received at least one prior therapy for their disease. In this study, high-risk was defined as having any one or more of the following: 17p deletion, 11q deletion or p53 mutation.

The study was conducted at 160 clinical trial sites in the US and Israel and randomized 126 patients. Patients received ibrutinib orally at 420 mg once daily in both arms and in the treatment arm those patients also received intravenous infusions of ublituximab at 900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6. Patients in the treatment arm who had not progressed received quarterly infusions of ubltuximab maintenance at 900 mg.

On October 24, 2019 Baxter International Inc. (NYSE:BAX), a leading global medical products company, reported certain preliminary operating results for the quarter ended September 30, 2019 (Press release, Baxter International, OCT 24, 2019, View Source [SID1234542501]). Baxter further indicated that the Company is investigating misstatements in previously reported non-operating income. The internal investigation is described in further detail below.

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"Our strong preliminary operating results reflect the positive impact of Baxter’s ongoing transformation, commitment to innovation and continued operational excellence," said José (Joe) E. Almeida, chairman and chief executive officer. "While the Company is working diligently and expeditiously to address the non-operating related accounting issue, Baxter’s 50,000 employees remain intently focused on our Mission to Save and Sustain lives as well as executing on our strategy to deliver top quartile performance for all stakeholders."

Preliminary Third Quarter Operating Results

Worldwide sales in the third quarter totaled approximately $2.85 billion, an increase of 3% on a reported basis, and 5% on both a constant currency and operational basis. Operational sales exclude the impact of foreign exchange and generic competition for U.S. cyclophosphamide.

Sales in the U.S. totaled $1.2 billion and International sales totaled $1.6 billion. All Baxter geographic regions contributed to positive sales performance in the quarter. Sales in the Americas were $1.5 billion, sales in Europe, Middle East and Africa (EMEA) were $730 million, and sales in Asia Pacific (APAC) were $587 million.

Key performance drivers in the third quarter included strong sales of Baxter’s peritoneal dialysis (PD) and continuous renal replacement therapies (CRRT), intravenous (IV) infusion systems and solutions, hemostats and sealants, and certain generic injectable pharmaceuticals. In addition, increased international demand for Baxter’s hospital pharmacy compounding services contributed to the strong performance in the quarter. As expected, revenues were partially offset by lower U.S. sales of Brevibloc and in-center hemodialysis (ICHD) products.

Please see the attached schedules accompanying this press release for additional details on performance in the quarter, including sales by Baxter’s six global business units.

Baxter reported operating income of $503 million for the third quarter. This includes special items totaling $52 million, primarily related to intangible asset amortization and business optimization initiatives, partially offset by insurance recoveries related to the impact of Hurricane Maria. On an adjusted basis, Baxter’s third quarter operating income totaled $555 million, or 19.5% of sales, reflecting strong revenues and solid operational performance.

Business Highlights2

Baxter continues to achieve significant milestones in pursuit of its Mission for patients and emphasis on accelerating profitable growth. Among recent highlights, the Company:

Initiated the U.S. and Canadian launches of Baxter’s next-generation PrisMax system for continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE). Among many advanced features, PrisMax incorporates TrueVue Analytics, Baxter’s proprietary data and analytics platform.
Announced the agreement to acquire Cheetah Medical, a leading provider of non-invasive hemodynamic monitoring technologies. Once completed, this acquisition will accelerate Baxter’s presence in the specialized patient monitoring space, expanding the portfolio with key technology used to guide fluid management based on individual patient needs.
Announced a partnership with COSMED srl to commercialize Q-NRG+, a metabolic monitoring device utilizing indirect calorimetry (IC) technology. IC is used to accurately measure resting energy expenditure (REE) – a patient’s caloric needs while at rest – and is recommended in guidelines from nutrition societies around the world.
Broadened its generic injectable pharmaceuticals portfolio with the U.S. launch of Myxredlin (Insulin Human in 0.9% Sodium Chloride Injection), the first and only ready-to-use insulin for IV infusion in the hospital and other acute care settings.
Announced new data associating the use of Baxter’s automated peritoneal dialysis (APD) cyclers and the Sharesource remote patient management platform with a 39% reduction in hospitalizations for home PD patients receiving care at Baxter Renal Care Services clinics in Colombia. The data also show the use of Sharesource is associated with a 54% reduction in the length of hospital stay for home dialysis patients requiring inpatient care. Sharesource is the most widely adopted telehealth platform globally for home dialysis and has helped manage approximately 10 million PD treatments in more than 40 countries.
The Company has also received multiple recognitions in recent months. Among them, Baxter was:

Named to the Dow Jones Sustainability Indices (DJSI) – DJSI World and DJSI North America – recognizing continued leadership in sustainability and corporate responsibility. Baxter has appeared on each of these lists since the introduction of the DJSI in 1999.
Recognized as a 2019 Top 10 Percent Inclusion Index Company, one of just 14 companies cited for superior achievement in creating an inclusive workplace as part of Diversity Best Practices’ annual Inclusion Index.
Honored by Working Mother magazine as one of its 2019 100 Best Companies, and one of its 2019 Best Companies for Dads.
Internal Investigation

Baxter recently began an investigation into certain intra-Company transactions undertaken for the purpose of generating foreign exchange gains or losses. These transactions used a foreign exchange rate convention historically applied by the Company that was not in accordance with generally accepted accounting principles and enabled intra-Company transactions to be undertaken after the related exchange rates were already known. The Company is being assisted in the investigation by experienced external counsel and consultants.

These intra-Company transactions resulted in certain misstatements in the Company’s previously reported non-operating income related to net foreign exchange gains. Within "Other (income) expense, net," the Company previously reported net foreign exchange gains of $8 million, $113 million, $28 million, $50 million, $73 million, and $22 million, for the years 2014, 2015, 2016, 2017, 2018, and the first half of 2019, respectively. The investigation is not limited to these periods and any subsequent adjustments to previously reported foreign exchange gains and losses may alter those non-operating income results.

The Audit Committee of the Company’s Board of Directors is overseeing this investigation with the assistance of independent, experienced external advisors. Baxter voluntarily advised the staff of the Securities and Exchange Commission (SEC) that the internal investigation is underway and intends to provide additional information to the SEC as the investigation progresses. The Company does not expect to file its quarterly report on Form 10-Q for the period ended September 30, 2019 on a timely basis.

The investigation is in its early stages and the Company cannot predict its duration or outcome. Upon completion of the investigation and the Company’s evaluation of the materiality of the misstatements, the Company expects to either amend its periodic reports previously filed with the SEC to include restated financial statements that correct those misstatements, or include in reports for future periods restated comparative financial statements that correct those misstatements. The Company also will consider the extent to which these matters impact the effectiveness of its internal control over financial reporting.

"Baxter takes this matter very seriously, and the Board along with the Company’s leadership team fully supports a comprehensive investigation," Mr. Almeida stated. "The Company is taking steps to strengthen and enhance its internal controls, and we look forward to sharing our full financial results as soon as possible."

As part of any corrections to previously issued financial statements after completion of the non-operating income investigation, Baxter also expects to correct certain items that affect operating income and were immaterial to its previously reported results of operations. These items include the impact of the use of the foreign exchange rate convention to translate the results of the Company’s foreign operations into U.S. dollars and the impact of the incorrect accounting for placed equipment that the Company leases to its customers. Correction of these immaterial misstatements would not affect the reported sales growth rate in the third quarter 2019 or the projected reported growth rate or projected operating margin range for the fourth quarter presented herein.

Fourth Quarter 2019 Sales and Operating Margin Outlook2

For the fourth quarter of 2019, the Company expects sales growth of 3-4% on a reported basis and approximately 5% on a constant currency and operational basis. Baxter expects operating margin to be between 15.2% and 15.9% on a reported basis and between 18.5% and 19% on an adjusted basis.

Conference Call Information

A webcast of Baxter’s third quarter 2019 conference call for investors can be accessed live from a link on the Company’s website at www.baxter.com beginning at 7:30 a.m. CDT on October 24, 2019. Please see www.baxter.com for more information regarding this and future investor events and webcasts.

On October 24, 2019 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with a focus on myelodysplastic syndromes (MDS), reported that the Company believes it remains on target to report top-line data from the global Phase 3 INSPIRE Trial with intravenous (IV) rigosertib in second-line, higher-risk MDS patients in the first half of 2020 following full enrollment and 288 death events (Press release, Onconova, OCT 24, 2019, View Source [SID1234542483]). The Company anticipates completion of the INSPIRE Trial in the first half of 2020 based on approaching 90 percent or 324 randomized patients of the required 360 randomized patients, and the number of confirmed death events reached to date.

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Steven M. Fruchtman, M.D., President and Chief Executive Officer, stated, "Enrollment in our global Phase 3 INSPIRE Trial with IV rigosertib in second-line, higher-risk MDS patients is progressing. We are approaching 90 percent of planned enrollment. Based on enrollment and the number of reported events reached, which exceeded 75% of the required 288 events at end of September 2019, we continue to anticipate reporting top-line data in the first half of 2020 following full enrollment and 288 death events. Enrollment in Brazil is expected to begin in November, and we look forward to the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy Congress in Rio de Janeiro, November 6-9."

Dr. Richard Woodman, Chief Medical Officer of Onconova, continued, "Prior to readout of the INSPIRE trial, the Company plans to focus Onconova’s research and development activities on completing the INSPIRE trial. After completion of the INSPIRE trial, based on recent feedback from the FDA, we plan to conduct a randomized Phase 2 Trial with a control arm of single agent azacitidine for the continued development of oral rigosertib plus azacitidine in first-line higher-risk MDS patients. We also plan to consult with key opinion leaders on the design of a Phase 2 controlled study for submission to the FDA as the next step in the development of oral rigosertib. The proposed Phase 2 Study does not require a Special Protocol Assessment (SPA)."

In addition to the pivotal Phase 3 INSPIRE study, a Phase 1 study of rigosertib in combination with a PD-1 inhibitor for patients with progressive K-Ras mutated non-small cell lung cancer is expected to commence by early 2020 as an investigator-initiated study. Ras-mutated cancers represent about a third of all human cancers. We recently participated in the RAS Drug Discovery Summit in Boston and plan to participate in the next RAS Drug Discovery Summit in Vienna, Austria in February 2020. We are also working toward filing an IND for a Phase 1 trial of ON 123300, our investigational dual inhibitor of CDK4/6 + ARK5, which we believe has the potential to treat various cancers including refractory metastatic breast cancer. The IND has been submitted in China by our corporate partner Han X.

On October 24, 2019 Compass Therapeutics, a clinical-stage biotechnology company focused on drugging the human immune synapse to treat human diseases, reported two upcoming poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2019 Annual Meeting, which is being held November 6-10 in National Harbor, MD (Press release, Compass Therapeutics, OCT 24, 2019, View Source [SID1234542502]).

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The first poster will show recent data on CTX-8371, a novel bispecific antibody targeting the inhibitory receptor PD-1 and its ligand, PD-L1. CTX-8371 was discovered in an unbiased screen of checkpoint bispecifics using Compass’s proprietary StitchMabsTM technology. CTX- 8371 demonstrates significantly increased potency in vitro and in vivo compared to combinations of monoclonals blocking PD-1 and PD-L1. Mechanistic studies of CTX-8371 suggest that the enhanced potency is associated with its unique ability to drive PD-1 downregulation from the surface of effector T cells.

The second poster presentation describes Compass’s innate-cell engager platform. Leveraging its common light-chain technology, Compass has developed a series of bispecific antibodies that simultaneously engage tumor associated antigens and the activating receptor NKp30 expressed on NK cells and other innate effector cells to promote potent and highly selective tumor cell killing.

Full details of the presentations are as follows:

Poster title: CTX-8371, a novel bispecific targeting both PD-1 and PD-L1, is more potent than combination anti-PD-1 and PD-L1 therapy and provides enhanced protection from tumors in vivo
Abstract ID: P251
Date & time: Friday, Nov. 8, 7:00 am – 8:00 pm ET
Location: Poster Hall (Prince George AB), Gaylord National Hotel & Convention Center, National Harbor, Md.

Poster title: A novel class of multi-specific antibodies targeting NKp30 on innate immune cells
Abstract ID: P7770
Date & time: Saturday, Nov. 9, 7:00 am – 8:00 pm ET
Location: Poster Hall (Prince George AB), Gaylord National Hotel & Convention Center, National Harbor, Md.

On October 24, 2019 AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, reported updated data from its ongoing glioblastoma Phase 2 clinical trial investigating AIVITA’s platform immunotherapy targeting tumor-initiating cells (Press release, AIVITA Biomedical, OCT 24, 2019, View Source [SID1234542467]). In approximately 80% of treated patients, sequential blood plasma biomarker analyses have identified the induction of a type II hypersensitivity response, followed by a dendritic cell-mediated antibody response. This immunological response is accompanied by decreased tumor load in approximately 81% of those same patients, equivalent to 65% of the total number of treated patients.

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Blood was collected from subjects at multiple time points, one week after each dose administration, and assayed for 450 different immune and tumor biomarkers. A robust type II hypersensitivity response was noted as an acute development at 2-3 weeks post-treatment, followed by dendritic cell maturation and the induction of an antibody-mediated response by 8 weeks post-treatment. Furthermore, the response is proportional to tumor load. The oncology literature associates this immunological profile with survival; indeed, 81% of the treated patients in the AIVITA study exhibiting this immunological profile also show a decrease of tumor markers.

"Blood analyses indicate that the AIVITA immunotherapy, in the presence of tumor, triggers an acute cytotoxic hypersensitivity followed by an antibody-mediated response and tumor marker reduction," said Dr. Gabriel Nistor, Chief Science Officer at AIVITA. "While very encouraging, only time will truly validate whether the appropriate immune response and decreasing tumor markers translate into patient survival."

AIVITA is currently conducting three distinct clinical studies in the USA investigating its platform immunotherapy, in patients with ovarian cancer, glioblastoma and melanoma. AIVITA is also seeking conditional commercial approval of its melanoma treatment in Japan. AIVITA uses 100% of proceeds from the sale of its ROOT of SKIN skincare line to support the treatment of women with ovarian cancer.

CLINICAL TRIAL DETAIL

OVARIAN CANCER

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous tumor-initiating cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITA’s AVOVA-1 trial patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the tumor-initiating cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AIVITA’s tumor-initiating cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.