On June 15, 2019 AstraZeneca reported detailed results from the interim analysis of the Phase III ASCEND trial at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Amsterdam, showing Calquence (acalabrutinib) significantly prolonged the time patients live without disease progression in relapsed or refractory chronic lymphocytic leukaemia (CLL) (Press release, AstraZeneca, JUN 15, 2019, View Source [SID1234537099]).

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The ASCEND trial compared Calquence with the physician’s choice of rituximab combined with idelalisib (IdR) or bendamustine (BR) in patients with relapsed or refractory CLL.

At a median follow-up of 16.1 months, results from the trial showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) for patients treated with Calquence vs. IdR or BR, reducing the risk of disease progression or death by 69% (HR, 0.31; 95% CI, 0.20-0.49, p<0.0001). The median time without disease progression for patients treated with Calquence has not yet been reached vs. 16.5 months in the control arm. At 12 months, 88% of patients on Calquence showed no disease progression compared to 68% for the control arm. The safety and tolerability of Calquence was consistent with its established profile.

José Baselga, Executive Vice President, Oncology R&D said: "These data add to the growing body of evidence to support the profile of Calquence as a selective BTK inhibitor that offers a chemotherapy-free treatment option with a favourable safety profile in chronic lymphocytic leukaemia, a life-threatening disease. These data, along with our recent positive results from the Phase III ELEVATE-TN trial in previously-untreated chronic lymphocytic leukaemia, will serve as the foundation for regulatory submissions later this year."

Paolo Ghia, MD, Professor, Medical Oncology, Università Vita-Salute San Raffaele in Milan, and investigator of the ASCEND trial, said: "This is the first randomised trial to directly compare a BTK inhibitor as monotherapy with standard chemoimmunotherapy or idelalisib and rituximab combinations. With a significant improvement in progression-free survival and a favourable safety profile, acalabrutinib may become an important choice for the treatment of patients with relapsed or refractory chronic lymphocytic leukaemia."

Kaplan-Meier plot for PFS as assessed by an independent review committee in the intent-to-treat population1

calquence
Calquence (arm A) vs IdR or BR (arm B)

Calquence
*Secondary primary malignancy **Non-melanoma skin cancer.

AstraZeneca recently announced that the Phase III ELEVATE-TN trial met its primary endpoint at interim analysis in patients with previously-untreated CLL and that full results will be reported at a forthcoming medical meeting. Calquence is currently approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) in the US, Brazil, the United Arab Emirates, and Qatar and is being developed for the treatment of CLL and other blood cancers.

About ASCEND

ASCEND (ACE-CL-309) is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in previously-treated patients with CLL.2 In the trial, 310 patients were randomised (1:1) into two arms. Patients in the first arm received Calquence monotherapy (100mg twice daily until disease progression). Patients in the second arm received physician’s choice of either rituximab in combination with idelalisib or rituximab in combination with bendamustine.1,2

The primary endpoint is PFS assessed by an independent review committee (IRC), and key secondary endpoints include physician-assessed PFS, IRC- and physician-assessed overall response rate (ORR) and duration of response (DoR), as well as overall survival (OS), patient reported outcomes (PROs) and time to next treatment (TTNT).1,2

About Calquence

Calquence (acalabrutinib) was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Calquence is an inhibitor of Bruton tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.3 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in 26 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenstrom macroglobulinaemia, follicular lymphoma, and multiple myeloma and other haematologic malignancies. Beyond the positive Phase III trials ASCEND and ELEVATE-TN, other Phase III trials in CLL are ongoing, including ELEVATE-RR (ACE-CL-006) evaluating acalabrutinib vs. ibrutinib in patients with previously-treated high-risk CLL, and ACE-CL-311 evaluating acalabrutinib in combination with venetoclax and with/without obinutuzumab in patients with previously-untreated CLL without 17p deletion or TP53 mutation.

About chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in adults, with an estimated 191,000 new cases globally and 20,720 new cases in the US annually, and prevalence that is expected to grow with improved treatment.4-7 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.4 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.4 This could result in anaemia, infection and bleeding.4 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

About AstraZeneca in haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company’s haematology franchise includes two US FDA-approved medicines and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

In October 2018, AstraZeneca and Innate Pharma announced a global strategic collaboration that included Innate Pharma licensing the US commercial rights of Lumoxiti (moxetumomab pasudotox-tdfk), and with support from AstraZeneca, will continue EU development and commercialisation, pending regulatory submission and approval.

About AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines

On June 14, 2019 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported data for the first time from the ongoing Phase 1 Zella 101 study evaluating the safety and clinical activity of alvocidib, a potent CDK9 inhibitor, in combination with cytarabine and daunorubicin in patients with newly diagnosed acute myeloid leukemia (AML) (Press release, Tolero Pharmaceuticals, JUN 14, 2019, View Source [SID1234537097]). These results were presented in a poster presentation at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), being held June 13-16, 2019 in Amsterdam, The Netherlands.

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Preliminary data from the study indicated that alvocidib in combination with cytarabine and daunorubicin has shown clinical activity with acceptable safety in patients with newly diagnosed AML. Of the 18 evaluable patients, more than three-quarters (78%, n=14) achieved a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi). Of these patients attaining a CR/CRi, 78% (n=11) reached the 30-day post-study evaluation, per the study protocol. A subset of these patients, 27% (n=3 of 11) proceeded to stem cell transplant. Additionally, among adverse cytogenic risk patients (n=9) who generally respond poorly to induction therapy, two-thirds (67%, n=6 of 9), achieved a CR/CRi.1

Of the patients that attained a CR/CRi (n=14), 10 (71%) are still in remission with a median follow-up of 76 days. In addition, 21 of 22 (95%) enrolled patients are still alive, with a median follow-up of 70 days.

Adverse events (AEs) in the study include diarrhea, tumor lysis syndrome, infections and elevated AST levels and were consistent with those noted in previous alvocidib studies.1

"These preliminary data from the Zella 101 study in patients with newly diagnosed AML are encouraging, as they add to the growing body of evidence from the alvocidib clinical program," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals. "We look forward to continuing this study to further our understanding of how the combination of alvocidib with cytarabine and daunorubicin may benefit this patient population."

Additional data from Tolero’s pipeline will also be presented in an oral presentation at the meeting, highlighting the impact of investigational agent TP-0903, an oral AXL receptor tyrosine kinase (RTK) inhibitor, on Axl-RTK inhibition in patients with several tumors, including chronic lymphocytic leukemia (CLL).

Below are the details for the presentations:

Abstract Title

Details

Zella 101: Phase 1 Study of Alvocidib
Followed by 7+3 Induction in Newly
Diagnosed AML Patients

Abstract # PF285

June 14, 5:30-7 p.m. CEST

Poster Presentation

AXL-RTK Inhibition Directs the
Functional Phenotype of Chimeric
Antigen Receptor T Cells

Abstract # S909

June 15, 4-4:15 p.m. CEST

Oral Presentation

About Alvocidib
Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in a Phase II study, Zella 201, in patients with relapsed or refractory MCL-1 dependent acute myeloid leukemia, AML, in combination with cytarabine and mitoxantrone (NCT02520011). Alvocidib is also being evaluated in Zella 101, a Phase I clinical study evaluating the maximum tolerated dose, safety and clinical activity of alvocidib in combination with (7+3) in newly diagnosed patients with AML (NCT03298984), and Zella 102, a Phase 1b/2 study in patients with myelodysplastic syndromes, MDS, in combination with decitabine (NCT03593915). In addition, alvocidib is being evaluated in a Phase 1 study in patients with relapsed or refractory AML in combination with venetoclax (NCT03441555).

About CDK9 Inhibition and MCL-1
MCL-1 is a member of the apoptosis-regulating BCL-2 family of proteins.2 In normal function, it is essential for early embryonic development and for the survival of multiple cell lineages, including lymphocytes and hematopoietic stem cells.3 In MCL-1–dependent AML, MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.2,4 The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).5,6 Because of the short half-life of MCL-1 (2-4 hours), the effects of targeting upstream pathways are expected to reduce MCL-1 levels rapidly.5 Inhibition of CDK9 has been shown to block MCL-1 transcription, resulting in the rapid downregulation of MCL-1 protein, thus restoring the normal apoptotic regulation.2

On June 14, 2019 Ampio Pharmaceuticals, Inc. (NYSE American: AMPE) ("Ampio"), reported that it intends to offer and sell shares of its common stock in an underwritten public offering (Press release, Ampio, JUN 14, 2019, View Source [SID1234537096]). Ampio expects to grant the underwriters a 45-day option to purchase additional shares of common stock offered in the public offering. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Ampio intends to use the net proceeds from the proposed offering for working capital and general corporate purposes, including funding for its clinical trial (AP-013).

ThinkEquity, a division of Fordham Financial Management, Inc., is acting as sole book-running manager for the offering.

A shelf registration statement on Form S-3 (File No. 333-217094) relating to the shares of common stock to be issued in the proposed offering was filed with the Securities and Exchange Commission (SEC) and is effective. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

A preliminary prospectus supplement and accompanying prospectus describing the terms of the proposed offering will be filed with the SEC. The securities may be offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the securities being offered may also be obtained from ThinkEquity, a division of Fordham Financial Management, Inc., 17 State Street, 22nd Floor, New York, New York 10004, by telephone at (877) 436-3673, by email at [email protected]. Electronic copies of the preliminary prospectus supplement and accompanying prospectus will also be available on the SEC’s website at View Source

Safe Harbor

This press release contains forward-looking statements regarding the proposed public offering and the intended use of proceeds from the offering. The offering is subject to market and other conditions and there can be no assurance as to whether or when the offering may be completed or as to the actual size or terms of the offering. Forward-looking statements involve known and unknown risks, uncertainties and other factors that could cause actual results to differ materially, including those risks disclosed in under the caption "Risk Factors" in the preliminary prospectus supplement related to the offering and our Annual Report on Form 10-K filed with the SEC on March 18, 2019, our Quarterly Report on Form 10-Q filed with the SEC on May 10, 2019 and our other filings with the SEC. Ampio Pharmaceutcials, Inc. cautions readers not to place undue reliance on any forward-looking statements and it does not undertake, and specifically disclaims any obligation, to update

On June 14, 2019 Flatiron Health reported that Dr. Michael Vasconcelles, a practicing oncologist and senior biotechnology and pharmaceutical executive, has joined as Chief Medical Officer, effective August 2019 (Press release, Flatiron Health, JUN 14, 2019, View Source [SID1234537095]). Dr. Vasconcelles will be responsible for defining and executing the company’s strategic vision for real-world evidence, providing thought leadership and guidance around novel clinical research methods, and partnering with clients and stakeholders, including government agencies, to further the use of real-world data derived from electronic health records.

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"As an industry, we are seeing rigorous discussions, development of standards and concrete applications of real-world data for cancer research," said Zach Weinberg, COO and co-founder, Flatiron Health. "Dr. Vasconcelles’s deep clinical, development and regulatory experience will help drive these efforts industry-wide, and we are excited to bring that experience to bear so we can continue to serve our partners and patients across the oncology landscape."

As Chief Medical Officer, Dr. Vasconcelles will work cross-functionally to drive the overall strategy and execution of Flatiron’s research business. Dr. Vasconcelles will focus on Flatiron’s research, quality and regulatory offerings, and Dr. Bobby Green will continue to serve as Chief Medical Officer focusing on the clinical development of Flatiron’s suite of technology and services for community oncology.

"We are at a defining moment in oncology, where cancer research and clinical treatment are informing one another, driving a holistic learning healthcare system," said Dr. Michael Vasconcelles. "Flatiron has been at the forefront of developing real-world data for cancer research, and I am excited at the opportunity to be able to contribute to their mission of improving lives by learning from the experience of every cancer patient."

Dr. Vasconcelles most recently served as chief medical officer at Unum Therapeutics, a Cambridge-based oncology biotech focused on developing engineered autologous T cells for the treatment of cancer. Previously, as a member of their respective oncology business unit and R&D management teams, Dr. Vasconcelles was directly accountable for the research and development strategy and execution at Takeda/Millennium and Genzyme for their oncology portfolios, from discovery through product licensure and post approval. Following Sanofi’s acquisition of Genzyme, Dr. Vasconcelles joined Sanofi Oncology as head of the personalized medicine and companion diagnostics division.

Dr. Vasconcelles currently serves as a clinical instructor in medicine at Harvard Medical School, where he has taught since 1996, and is a practicing oncologist and associate physician at the Dana-Farber Cancer Institute and Brigham & Women’s Hospital in Boston.

Flatiron’s former chief medical officer, Dr. Amy Abernethy, joined the U.S. Food & Drug Administration as principal deputy commissioner in early 2019.

To learn more about Flatiron, visit www.flatiron.com or follow us @FlatironHealth.

On June 14, 2019 Mawdsleys and Meabco A/S reported that have launched a Named Patient Supply program to allow Oncologists within the European Union (EU) to obtain access to BP-C1 on an unlicensed basis for the treatment of metastatic breast cancer and incurable pancreatic cancer (Press release, Meabco, JUN 14, 2019, View Source [SID1234537094]).

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BP-C1 is a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride developed for patients suffering from metastatic breast cancer

The Named Patient Supply program for the EU will allow physicians early access to BP-C1 for their patients. Mawdsleys’ Director of Specialty Pharma, David Regan, comments "We are pleased to be working with Meabco to add BP-C1 to our growing portfolio of oncology and rare disease medicines which Mawdsleys can make available on an early access basis to help provide new treatment options to patients with serious unmet medical needs."

Healthcare professionals can obtain further details about the BP-C1 Named Patient Supply program using the contact details below.

NOTES TO EDITORS

About BP-C1

BP-C1 is an anti-neoplastic agent with palliative properties and is based on Meabco’s patented polyphenolic technology platform. BP-C1 offers a combination of immunomodulation and tumor control in one product. Usually, immunomodulation and tumor control are obtained separately by using two or more drugs.

BP-C1 has been tested in a wide range of animal trials as well as in human phase II clinical trials. The safety profile is high with very low toxicity. BP-C1 acts apoptotic, anti-proliferative and anti-angiogenic on tumor cells, while at the same time contributing to anti-cancer immune regulatory activities. Opposite to other kind of chemotherapy, BP-C1 is given as one daily intramuscular injection in the outpatient clinic or at home by a nurse or the patient himself.

BP-C1 has been tested in close to 300 breast and pancreatic cancer patients in seven countries with promising results. It is noteworthy, that more than 80% of breast cancer patients and more than 60% of pancreatic cancer patients responded to the therapy. BP-C1 is aimed at fighting the cancer combined with strengthening the body’s immune system.