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Senhwa Biosciences Reports Positive Phase 1 Data of CX-5461 in Patients With Advanced Solid Tumors at 2019 SABCS

On December 12, 2019 Senhwa Biosciences Inc. (TPEx: 6492), a clinical stage biopharmaceutical company focused on next generation DNA Damage Response (DDR) therapeutics for the treatment of cancer, reported positive results from its Phase 1 trial of CX-5461. CX-5461 is the company’s First-in-Class G-quadruplex stabilizer (Press release, Senhwa Biosciences, DEC 12, 2019, View Source [SID1234552331]). The patients enrolled in the study all presented with advanced solid tumors, with no other available treatment options.

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In 2016, CX-5461 was awarded a Stand Up to Cancer Dream Team Grant. Phase 1 clinical findings were featured within a spotlighted presentation at the annual 2019 San Antonio Breast Cancer Symposium (SABCS) by Senhwa’s clinical partner, Canadian Cancer Trials Group (CCTG).

"CX-5461 has demonstrated clinically meaningful and durable benefits in patients with specific tumor biomarkers that are also resistant to platinum and other chemotherapeutics. The Phase 1 study has validated CX-5461 as a G-quadruplex stabilizer within a novel class of therapy that accelerates dsDNA breaks and has proven human efficacy across certain tumor types," said Dr. Tai-Sen Soong, CEO of Senhwa Biosciences. The clinical results exhibited that CX-5461 has the potential to rescue cancer patients who have developed resistance to platinum and other chemotherapeutics. Additional clinical trials are being planned to further confirm the efficacy seen.

The Phase 1 dose escalation portion of the CX-5461 trial was designed to determine Recommended Phase 2 Dose (RP2D), as well as evaluate preliminary anti-tumor activity of a single agent (CX-5461), in patients with metastatic and recurrent solid tumors. 41 patients enrolled in the study, due to the fact that all available treatments had failed to treat their malignancies, and 40 of those patients had been treated with different dose levels of CX-5461.

As of the November 25th, 2019 data cutoff, the study findings showed:

32 of 41 patients enrolled were evaluable patients, the median age was 53 (range 25-73).
Of the evaluable patients, 24 had attempted 3 or more prior treatment regimens for their disease.
In this heavily pre-treated Phase 1 population, responses were seen with CX-5461 within the dose range of 100mg/m2 to 650mg/m2.
Patients presented with a range of solid tumors, including metastatic breast cancer (47.5%), Ovary (17.5%), Pancreas (7.5%), Non-small-cell Lung Cancer (5%) and others (22.5%)
Preliminary Safety Analysis:

CX-5461 was well tolerated:
– Treatment-related Adverse Events (AEs ≥20%) were photosensitivity of the skin (58%); eye disorders (including Photosensitivity 20%); nausea (70%); headache (25%); fatigue (73%).
– No Dose Limited Toxicities (DLTs) observed to date. There were 6 treatment-related non-DLT grade 3 photosensitivity events.
– The RP2D was determined to be 475mg/m2 on days 1, 8 and 15 of a 4-week cycle.
UV avoidance and protection measures were successful in mitigating risks associated with photo toxicity.
Preliminary Efficacy Analysis:

As of the data cutoff, 32 patients were evaluable for response. In terms of best response, 4 patients (3 breast cancer, 1 ovary) had a confirmed Partial Response with an additional 4 patients had durable Stable Disease.
Heavily pre-treated (including platinum resistant) patients with specific biomarkers showed significant tumor shrinkage and maintained significant treatment duration in the trial. The maximum duration was 16 cycles, with 28 days per cycle.
G-quadruplex stabilizers are a novel class of therapy that has demonstrated accelerated dsDNA breaks.
About CX-5461

CX-5461 is designed to stabilize DNA G-quadruplexes of cancer cells and leads to disruption of the cell’s replication fork. While acting in concert with HR (Homologous Recombination) pathway deficiency, such as BRCA1/2 mutations, replication forks stall and cause DNA breaks, resulting in cancer cell death. CX-5461 in combination with HRD (Homologous Recombination Deficiency) tumors may be exploited through a synthetic lethality approach, targeting DNA repair defects in HRD tumors.

Centene Corporation Announces 2020 Guidance

On December 12, 2019 Centene Corporation (NYSE: CNC) reported its 2020 financial guidance (Press release, Centene , DEC 12, 2019, View Source [SID1234552330]). Total revenues are expected to be $78.6 billion to $79.4 billion, and diluted earnings per share are expected to be $4.17 to $4.33. Adjusted diluted earnings per share for 2020 are expected to be $4.64 to $4.84.

For its 2020 fiscal year, the Company’s guidance is as follows:

Total revenues in the range of approximately $78.6 billion to $79.4 billion.
Diluted earnings per share of approximately $4.17 to $4.33.
Adjusted diluted earnings per share of approximately $4.64 to $4.84.
Health benefits ratio of approximately 86.0% to 86.5%.
Selling, general and administrative (SG&A) expense ratio of approximately 9.2% to 9.7%.
Adjusted SG&A expense ratio of approximately 9.1% to 9.6%, which excludes $15 million to $25 million of acquisition related expenses.
Effective tax rate of approximately 34.0% to 36.0%.
Diluted shares outstanding of approximately 422.5 million to 424.5 million.
"We are on track to close another successful year at Centene, as a result of strong execution across our product and market portfolio," said Michael Neidorff, Chairman, President and CEO of Centene. "We look ahead at 2020 well-positioned to continue to deliver on our growth strategy with strong top and bottom-line performance. It will be a transformational year for Centene as we look forward to completing the WellCare transaction and solidify our place as the premier government-sponsored healthcare enterprise. We remain focused on enhancing our ability to serve our members and improving their health, while creating significant value for our shareholders."

The Company’s 2020 guidance excludes the pending WellCare acquisition, associated one-time integration costs, the related financing and closing costs, and the impact of the previously announced divestitures. The acquisition is subject to regulatory approval and is expected to close in the first half of 2020. The Company’s 2020 guidance includes acquisition related expenses of $15 million to $25 million for legal and integration planning expenses. Additionally, our 2020 guidance reflects a delay in the North Carolina start date from February 1, 2020 to October 1, 2020, resulting in a reduction of revenues of approximately $500 million and diluted earnings per share of approximately $0.06.

The Company affirms its 2019 total revenues guidance in the previously announced range of $73.6 billion to $74.2 billion, updates its 2019 diluted earnings per share guidance to a range of approximately $3.01 to $3.18, and affirms its 2019 adjusted diluted earnings per share guidance of approximately $4.29 to $4.49. The 2019 diluted earnings per share guidance was decreased by $0.03 to reflect the net carrying cost of the $7.0 billion issuance of senior notes completed in December in preparation for the WellCare acquisition. The net carrying costs include the related interest expense and corresponding investment income. Full year 2019 earnings will be reported on February 4, 2020, at 6:00 AM, with a conference call at 8:30 AM (Eastern Time).

Investor Meeting

Centene Corporation will host an investor meeting tomorrow at the Pierre Hotel in New York City, including a question-and-answer session, to discuss the details of its guidance. The event will begin promptly at 8:30 AM (Eastern Time) and end at approximately 12:30 PM (Eastern Time). Investors and other interested parties who are unable to attend in person are invited to listen to the investor meeting via a live, audio webcast on the Company’s website and view a copy of the investor presentation at www.centene.com, under the Investors section.

Non-GAAP Financial Presentation

The Company is providing certain non-GAAP financial measures in this release as the Company believes that these figures are helpful in allowing investors to more accurately assess the ongoing nature of the Company’s operations and measure the Company’s performance more consistently across periods. The Company uses the presented non-GAAP financial measures internally to allow management to focus on period-to-period changes in the Company’s core business operations. Therefore, the Company believes that this information is meaningful in addition to the information contained in the GAAP presentation of financial information. The presentation of this additional non-GAAP financial information is not intended to be considered in isolation or as a substitute for the financial information prepared and presented in accordance with GAAP. The Company references Adjusted SG&A Expense Ratio guidance, however the Company cannot provide a reconciliation of Adjusted SG&A Expense Ratio guidance without unreasonable efforts. As such, it has been excluded from the reconciliation below.

Specifically, the Company believes the presentation of non-GAAP financial information that excludes amortization of acquired intangible assets, acquisition related expenses, as well as other items, allows investors to develop a more meaningful understanding of the Company’s performance over time. The table below provides reconciliations of non-GAAP items per share:

Annual Guidance December 31, 2019

The amortization of acquired intangible assets per diluted share presented above are net of the income tax benefit of an estimated $0.14 for the year ended December 31, 2019 and $0.13 to $0.14 for the year ended December 31, 2020.

The acquisition related expenses per diluted share presented above are net of the income tax benefit of an estimated $0.07 for the year ended December 31, 2019 and an estimated $0.01 to $0.02 for the year ended December 31, 2020. Acquisition related expenses for 2019 include net carrying costs on the $7.0 billion senior notes issued in preparation of the WellCare acquisition of approximately $15 million, or $0.03 per diluted share, net of an income tax benefit of approximately $0.01.

Other adjustments for 2019 include the following: non-cash goodwill and intangible asset impairment of $271 million or $0.57 per diluted share, net of an income tax benefit of $0.08 and debt extinguishment costs of $29 million or $0.05 per diluted share, net of an income tax benefit of approximately $0.02.

Oncternal Therapeutics Announces Presentation of Interim Clinical Data on Cirmtuzumab in Combination with Paclitaxel at 2019 San Antonio Breast Cancer Symposium

On December 12, 2019 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the presentation of interim data from the ongoing, investigator-sponsored Phase 1b clinical study of cirmtuzumab, its investigational anti-ROR1 monoclonal antibody, in combination with paclitaxel in patients with HER2-negative, metastatic or locally-advanced unresectable breast cancer (Press release, Oncternal Therapeutics, DEC 12, 2019, View Source [SID1234552329]). The results were presented at the San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX. A copy of the poster presentation is available online at www.oncternal.com.

As of the data cut-off date of November 27, 2019, a total of eight patients with HER2-negative, metastatic or locally-advanced unresectable breast cancer were enrolled in the study. Seven of the eight patients were evaluable for safety and efficacy. Four of the patients had triple negative breast cancer (TNBC) at study enrollment.

Four of the seven evaluable patients achieved a partial response, for an objective response rate of 57%, including one partial response that continued on cirmtuzumab alone for 30 weeks after discontinuing paclitaxel.

The combination of cirmtuzumab and paclitaxel has been well tolerated in this trial, with no study discontinuations for toxicity and no dose-limiting toxicities observed to date. Adverse events have been consistent with the known safety profile of paclitaxel alone.

Pharmacokinetic analysis of serial plasma samples for free unbound antibody from two patients provided results similar to those observed in previous studies of chronic lymphocytic leukemia patients, consistent with a projected half-life of 30 days. No decline in antibody concentration over time was observed, consistent with the absence of neutralizing antibodies.

"It is encouraging to see that cirmtuzumab in combination with paclitaxel has been well tolerated and is active. Future studies will determine whether cirmtuzumab is contributing to the known activity of paclitaxel. Advanced breast cancer patients are in need of improved treatment options with acceptable side effects. We look forward to completing enrollment and treating additional patients in this study," said Rebecca Shatsky, M.D., Assistant Clinical Professor, Medicine at University of California San Diego School of Medicine, lead investigator who presented the poster.

Funding for this trial was provided by Oncternal Therapeutics, California Institute for Regenerative Medicine, UC San Diego Alpha Stem Cell Clinic and Sanford Stem Cell Clinical Center, UC San Diego Moores Cancer Center, Padres Pedal the Cause Grant, and Gonick Breast Cancer Research Funds.

"The early activity signals for cirmtuzumab in combination with paclitaxel for patients with breast cancer seen in this study are encouraging. We believe these data, taken together with the previously updated clinical data in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) from the CIRLL study presented at the annual ASH (Free ASH Whitepaper) meeting, reinforce the encouraging safety data and provide evidence of clinical activity of cirmtuzumab and its potential for the treatment of patients with breast cancer and other ROR1-expressing solid tumors and hematological malignancies," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO.

About the Clinical Trial

This clinical trial is an investigator-sponsored Phase 1b Pilot Clinical Trial of Cirmtuzumab, an Anti-ROR1 Monoclonal Antibody, in Combination with Paclitaxel for the Treatment of Patients with Metastatic, or Locally Advanced, Unresectable Breast Cancer. The objectives of the trial include the evaluation of safety, tolerability, pharmacokinetics, and clinical activity. Eligible patients are those with locally-advanced, unresectable or metastatic HER2-negative breast cancer who had not received paclitaxel in the metastatic setting. Study treatment included a fixed dose of 600 mg cirmtuzumab given on days 1 and 15 of cycle 1, and then on day 1 of each subsequent 28-day cycle. Paclitaxel was given weekly at a dose of 80 mg/m2. Additional information about the clinical trial may be accessed at ClinicalTrials.gov (NCT02776917).

About Cirmtuzumab

Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL or MCL, in a collaboration with the UC San Diego School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the UC San Diego School of Medicine. CIRM has also provided funding to support development programs for cirmtuzumab and a CAR-T therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors.

ROR1 is a potentially attractive target for cancer therapy because it is an oncofetal antigen – a protein that confers a survival and fitness advantage when reactivated and expressed by tumor cells. When expressed by hematologic malignancies such as CLL and MCL, ROR1 acts as a receptor for the tumor growth factor Wnt5a. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to inhibiting Wnt5a activation, specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. Cirmtuzumab is in clinical development and has not been approved by the U.S. Food and Drug Administration for any indication.

Physicians’ Education Resource® Presents the 17th Annual Winter Lung Cancer Conference™

On December 12, 2019 Physicians’ Education Resource (PER), the nation’s leading resource for oncology and hematology continuing medical education (CME), reported that it will host the 17th Annual Winter Lung Cancer Conference, Feb. 7-9, 2020, at Eden Roc Miami Beach in Miami Beach, Florida (Press release, Physicians’ Education Resource, DEC 12, 2019, View Source [SID1234552328]).

"We know this one-of-a-kind meeting will be one of the premier educational events to learn state-of-the-art care for patients with lung cancers," said Phil Talamo, president of PER. "Our world-class CME conference not only allows our participants to learn, but to share their personal experiences and best practices in lung cancer management."

The historic Winter Lung Cancer Conference will be co-chaired by Rogerio C. Lilenbaum, M.D., professor of medicine in medical oncology and chief medical officer of Smilow Cancer Hospital, Yale New Haven Health; Mark A. Socinski, M.D., executive medical director at Florida Hospital Cancer Institute and AdventHealth Cancer Institute; Heather A. Wakelee, M.D., professor of medicine (oncology) at Stanford University Medical Center; and Julie R. Brahmer, M.D., M.Sc., FASCO, co-director, upper aerodigestive department, Bloomberg-Kimmel Institute for Cancer Immunotherapy; director, thoracic oncology program, professor of oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

For 17 years, the Winter Lung Cancer Conference has brought together world-class thoracic oncologists to share the best practices in the treatment of lung cancers. During this two-day program, attendees will have the chance to learn from and interact with international experts in several therapeutic areas, including immunotherapy, targeted agents, and multidisciplinary approaches. This conference provides the most cutting-edge research and practical information for the care of their patients, as well as offer a preview of new agents and techniques that will inform the future of lung cancer treatment. Throughout the program, question-and-answer sessions will also provide attendees with the opportunity to consult with faculty and their community-based peers.

Osaka University and Fuzionaire Radioisotope Technologies K.K. to Jointly Develop Astatine-211 Radiopharmaceuticals and Fluorine-18 Radiotracers for Oncology

On December 12, 2019 Fuzionaire Radioisotope Technologies K.K. ("FRIT"), a Japanese affiliate of radiopharmaceutical company Fuzionaire Diagnostics, Inc. ("Fuzionaire Dx"), reported a collaborative research agreement with the Department of Nuclear Medicine and Tracer Kinetics at Osaka University Graduate School of Medicine (Press release, Osaka University, DEC 12, 2019, View Source [SID1234552327]). The collaboration will use Fuzionaire Dx’s proprietary chemistry and Osaka’s unique clinical and radiochemistry capabilities to accelerate the discovery of novel anti-cancer radiotherapeutic agents.

The joint research effort aims to produce therapeutic molecules that contain astatine-211, a radioactive isotope, as the tumor-destroying payload. Astatine-211 emits alpha particles, which have enough energy to destroy cells. Unlike available treatments that emit beta particles, alpha particles penetrate a very limited distance, typically a depth of only a few cells. This makes it possible for alpha particles to treat isolated cancer cells, disseminated tumors, micrometastases, and supplement conventional therapies that may leave undetectable tumors that could lead to a recurrence. The initial research collaboration aims to identify clinical candidates for different oncology indications.

The collaboration will also further explore Fuzionaire Dx’s fluorine-18 radiochemistry platform, which can produce radiopharmaceuticals that identify and localize cancerous tissue in positron emission tomography (PET) scans prior to radiotherapeutic intervention, enabling better treatment stratification and monitoring of patient response.

"The Department of Nuclear Medicine and Tracer Kinetics at Osaka University Graduate School of Medicine is one of Japan’s leading nuclear medicine departments, with particular expertise in alpha nuclides for cancer therapy," said FRIT CEO Hiroshi Nakashita, MD. "We look forward to collaborating with leaders in the field on work that could greatly improve outcomes for patients with cancers that are difficult to treat using existing methods."

Primary leadership for the scientific collaboration includes Tadashi Watabe, MD, PhD, Assistant Professor in the Department of Nuclear Medicine and Tracer Kinetics at Osaka University Graduate School of Medicine, and Anton Toutov, PhD, Chief Science Officer of Fuzionaire Dx.

"We are very pleased to be working with the Fuzionaire team," said Professor Tadashi Watabe, project research lead at Osaka. "This collaborative research agreement is consistent with our department’s vision to become a pipeline of drug development, moving our research from the laboratory into clinical trials."

Anton Toutov, PhD, Chief Science Officer of Fuzionaire Dx, added, "There are unique chemistry challenges associated with the synthesis of astatine-211 and fluorine-18 radiopharmaceuticals, and our insights in this area are among the technological foundations of our company. We are excited to combine Osaka’s clinical capabilities and infrastructure with our expertise and technology to develop treatments and diagnostics to impact cancer care."

About Nuclear Medicine at Osaka University

The Integrated Radiation Laboratory at Osaka University Graduate School of Medicine is an interdisciplinary environment combining the use of diagnostic imaging techniques (PET and SPECT) as well as new application areas in therapeutic radiation oncology and radioactive isotopes. The team has the resources and personnel to explore novel radiopharmaceuticals from pre-clinical models to application in clinical practice. The laboratory was led by Professor Jun Hatazawa, one of Japan’s leading nuclear medicine physicians and current President of Asia Oceania Federation of Nuclear Medicine and Biology.