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Circle Pharma raises $45 Million in Series B Financing

On March 17, 2020 Circle Pharma, Inc., a macrocycle drug discovery and development company focused on intractable cancer targets, reported that it has raised $45 million in a Series B financing (Press release, Circle Pharma, MAR 17, 2020, View Source [SID1234555639]).

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The financing was led by The Column Group, with participation by Nextech Invest. All investors from the prior round – ShangPharma, LifeForce Capital, and the Berkeley Catalyst Fund – joined the financing.

In conjunction with the financing, Peter Svennilson, founder and managing partner of The Column Group, and Thilo Schroeder, Ph.D., partner at Nextech Invest were appointed to the board. John Josey, Ph.D., formerly President and CEO of Peloton Therapeutics, was appointed to the board as Chairman.

Proceeds from the investment will be used to advance Circle’s work to develop inhibitors of Cyclin A and Cyclin E, and to expand the company’s pipeline.

"We are delighted to have these premier life science investors supporting our Series B financing" said David J. Earp, J.D., Ph.D., Circle’s President and CEO. "With this strong backing, we will expand our team, drive our cyclin targeted programs towards the clinic, and apply our macrocycle platform to additional intractable targets."

Circle’s new board appointments:

Peter Svennilson is the founder and managing partner of The Column Group. He was the chairman of Aragon Pharmaceuticals (acquired by Johnson & Johnson) and Seragon Pharmaceuticals (acquired by Roche / Genentech) and was a board director of Gritstone Oncology, NGM Biopharmaceuticals, Immune Design and Constellation Pharmaceuticals. He is currently a board director of ORIC Pharmaceuticals, Ribon Therapeutics and Carmot Therapeutics.

Thilo Schroeder, Ph.D., is a partner at Nextech Invest, a Zurich-based oncology-focused investment firm. He previously served on the board of Peloton Therapeutics (acquired by Merck) and Blueprint Medicines. He is currently a board director at IDEAYA Biosciences, Revolution Medicines, PMV Pharma, Silverback Therapeutics and a board observer at Black Diamond Therapeutics.

John Josey, Ph.D., served as the President, Chief Executive Officer, and member of the Board of Directors at Peloton Therapeutics from 2013 until its acquisition by Merck in 2019. From 2011 to 2013, he was President and Chief Scientific Officer at Peloton, and from 1998 to 2011, Vice President of Discovery Chemistry at Array Pharma.

The continuing members of Circle’s board of directors are Walter H. Moos, Ph.D., CEO of ShangPharma Innovation and Managing Director of Pandect Bioventures, Matthew P. Jacobson, Ph.D., Circle Pharma co-founder, chair of the department of pharmaceutical chemistry at U.C. San Francisco and also co-founder of Global Blood Therapeutics, Relay Therapeutics and Cedilla Therapeutics, and David J. Earp, J.D., Ph.D., President and Chief Executive Officer of Circle Pharma.

Blue Earth Diagnostics Announces Dosing of First Patient in Phase 3 LIGHTHOUSE Clinical Trial of Targeted PET Imaging Agent rhPSMA-7.3 (18F) in Newly Diagnosed Prostate Cancer

On March 17, 2020 Blue Earth Diagnostics, a Bracco company focused on molecular imaging diagnostics, reported that the first patient has been dosed in its Phase 3 LIGHTHOUSE clinical trial of rhPSMA-7.3 (18F), an investigational Prostate Specific Membrane Antigen-targeted radiohybrid PET imaging agent (Press release, Blue Earth Diagnostics, MAR 17, 2020, View Source [SID1234555638]). The LIGHTHOUSE study is a Phase 3, multi-center, single-arm imaging study being conducted in the United States and Europe to evaluate the safety and diagnostic performance of rhPSMA-7.3 (18F) PET imaging in men with newly diagnosed prostate cancer (NCT04186819). The primary objectives of the LIGHTHOUSE study are to assess the sensitivity and specificity of rhPSMA-7.3 (18F) PET for detecting pelvic lymph node metastases compared to surgical pathology on a patient level. The first patient in the LIGHTHOUSE study was dosed in Los Angeles, Calif. at RadNet’s Liberty Pacific Advanced Imaging Center in conjunction with Tower Urology.

"We are excited to initiate this Phase 3 imaging trial of rhPSMA-7.3 (18F), with the hope that it may help address the needs of men with newly diagnosed prostate cancer," said Jonathan Allis, D. Phil., CEO of Blue Earth Diagnostics. "LIGHTHOUSE is part of our strategy to expand and advance a world-leading prostate cancer imaging portfolio, alongside our planned Phase 3 clinical trial investigating the use of rhPSMA-7.3 (18F) PET imaging in patients with an elevated Prostate-Specific Antigen (PSA) level after prior therapy. rhPSMA-7.3 (18F) and approved, commercially available Axumin (fluciclovine F 18) have unique and complementary mechanisms of action, and we believe both compounds may ultimately allow physicians and their patients flexibility in selecting the diagnostic agent most appropriate to each specific clinical situation."

"Effective staging of primary prostate cancer − determining its presence and whether it may have metastasized − is critical in assessing a patient’s prognosis and informing individual clinical management strategies," said Gerald L. Andriole, MD, the Robert K. Royce Distinguished Professor and Chief of Urologic Surgery at Washington University School of Medicine. "Up to 25% of prostate cancer patients may have detectable lymph node metastases, which are correlated with a risk for recurrence and associated overall survival. Conventional imaging techniques, such as MRI and CT, are limited in the information they may provide, particularly in high-risk primary prostate cancer, due to low sensitivity and specificity. Pelvic lymph node dissection (PLND), or pelvic lymphadenectomy, is considered the gold standard in assessing pelvic lesions, but its use is limited to the planned surgical area. An ideal staging technique for detecting metastatic disease should not only include the pelvic nodes but also more distant soft tissue and skeletal findings and be both sensitive and specific for identifying prostate cancer metastases. A number of investigational studies have reported promising diagnostic performance using PSMA-targeted PET agents, but none are approved and clinical use is limited to compassionate use and research protocols. The Phase 3 LIGHTHOUSE clinical study is designed to investigate the diagnostic performance of rhPSMA-7.3 (18F) PET imaging as a potential decision-making aid in assessing newly diagnosed disease."

"Prostate cancer is a leading cause of male cancer-related death worldwide, and we anticipate that eventually a large proportion of patients with prostate cancer may be eligible to undergo PSMA PET imaging to help stage their disease and inform subsequent treatment choices," said David Gauden, D.Phil., Chief Scientific Officer of Blue Earth Diagnostics. "Blue Earth Diagnostics acquired an exclusive license to a broad family of theranostic rhPSMA agents in 2018, which includes an exclusive option for therapeutic applications. Since that time, we have worked closely with the Technical University of Munich (TUM) and Scintomics to identify a lead imaging candidate for further development. We selected rhPSMA-7.3 (18F), a single isomer of rhPSMA-7 (18F), as the candidate for our Phase 3 imaging studies. In anticipation of imaging performance, production capacity and quality needs, we selected F18 as the radiolabeling isotope of choice for rhPSMA-7.3 PET imaging. The 110-minute half-life and energy of the F18 radioisotope enable high resolution PET scans; large batch production; consistent, centralized manufacturing; and efficient distribution and broad geographic availability independent of select individual hospitals – all of which are important considerations in facilitating broad availability of this cutting edge technology for prostate cancer patients."

"Results from the early clinical experience by TUM, including with rhPSMA-7.3 (18F) PET, in more than 1,000 prostate cancer patients were included in the Investigational New Drug (IND) submission for the LIGHTHOUSE trial," said Peter Gardiner, MB ChB, MRCP, FFPM, Chief Medical Officer of Blue Earth Diagnostics. "Some of that experience has recently been published online in the Journal of Nuclear Medicine. Retrospective analyses assessed the diagnostic performance, biodistribution and safety of rhPSMA-7 (18F) in primary prostate cancer and in biochemical recurrence after both radical prostatectomy and radiation therapy. Blue Earth Diagnostics is also conducting a Phase 1 clinical study in Finland to assess the safety, biodistribution and dosimetry of rhPSMA-7.3 (18F) in healthy volunteers and patients with prostate cancer."

About the LIGHTHOUSE Phase 3 Clinical Trial for rhPSMA-7.3 (18F)

The LIGHTHOUSE Phase 3 clinical trial is a prospective, Phase 3, multi-center, single-arm, imaging study investigating the safety and diagnostic performance of rhPSMA-7.3 (18F) Positron Emission Tomography (PET) in men with newly diagnosed prostate cancer. The study will enroll approximately 375 evaluable patients at clinical sites in the United States and Europe. The primary endpoints of the LIGHTHOUSE study are to assess the sensitivity and specificity of rhPSMA-7.3 (18F) PET for detecting pelvic lymph node metastases compared to surgical pathology on a patient level. Secondary endpoints will assess the safety of rhPSMA-7.3 (18F) in patients and determine inter- and intra-reader agreement of rhPSMA-7.3 (18F) scan interpretations by blinded independent readers. Additional information about the Phase 3 LIGHTHOUSE trial is available at www.clinicaltrials.gov (NC04186819).

About rhPSMA

rhPSMA-7.3 (18F) consists of a radiohybrid Prostate-Specific Membrane Antigen (PSMA)-targeted receptor ligand which attaches to and is internalized by prostate cancer cells, and is labeled with the 18F radioisotope for PET imaging. rhPSMA compounds can also be labeled with radioisotopes such as 177Lu and 225Ac for therapeutic use. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA imaging technology from Scintomics in 2018, with an option to therapeutic rights. rhPSMA originated from the Technical University of Munich, Germany, and has been utilized clinically under German legislation at the Department of Nuclear Medicine there for the diagnostic imaging of men with both primary and recurrent prostate cancer. rhPSMA compounds have not received regulatory approval.

NOTE: Axumin (fluciclovine F 18) injection is FDA-approved for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

This press release is intended to provide information about Blue Earth Diagnostics’ business in the United States and Europe. Please be aware that the approval status and product label for Axumin varies by country worldwide. For EU Axumin product information refer to: View Source;mid=WC0b01ac058001d124.

U.S. INDICATION AND IMPORTANT SAFETY INFORMATION ABOUT AXUMIN
INDICATION

Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Surface Oncology Announces First Patient Dosed in Clinical Trial of Immuno-Oncology Candidate SRF617

On March 17, 2020 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that it has initiated a Phase 1/1b clinical trial of its antibody candidate SRF617, which targets the immunosuppressive protein CD39 (Press release, Surface Oncology, MAR 17, 2020, View Source [SID1234555634]).

"Our comprehensive preclinical data indicate SRF617 is a potent inhibitor of CD39, which may play an important role in tumor growth and spread via the immunosuppressive ‘adenosine axis’," said Robert Ross, M.D., chief medical officer of Surface Oncology. "This study is designed to provide rapid evaluation of SRF617 via multiple arms, including as a monotherapy and in combination with both chemotherapy and other immuno-oncology agents. We believe CD39 presents an important opportunity to develop next-generation treatments for cancer, and we look forward to evaluating our hypotheses in the clinic."

The Phase 1/1b dose escalation study will initially enroll patients with advanced solid tumors, then focus on three combination arms, either with gemcitabine and abraxane, with anti-PD-1, or with AB928, an A2A/A2B small molecule inhibitor (in clinical collaboration with Arcus Biosciences (NYSE: RCUS)). Further planned cohorts will focus on several tumors of high unmet need, including pancreatic cancer, gastric cancer and tumors that have demonstrated resistance to anti-PD-1 therapy. A biopsy expansion cohort has been designed to provide data on changes in tumor tissue CD39 enzymatic activity related to SRF617 treatment. Surface expects to provide an initial clinical update from the dose escalation portion of the study by the end of 2020.

About SRF617
SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39, allowing for a dual mechanism of action to promote anti-tumor immunity via reduction of immunosuppressive adenosine in addition to increasing levels of immunostimulatory ATP. In preclinical studies, SRF617 has exhibited strong affinity for and inhibition of CD39, the ability to reduce adenosine and increase ATP levels, and anti-tumor activity both as a single agent and in combination with multiple therapeutic agents.

Kitov Closes $6.0 Million Public Offering

On March 17, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported the closing of its previously announced public offering of 20,000,000 units at a price to the public of $0.30 per unit, for gross proceeds of $6.0 million, before deducting placement agent fees and other offering expenses payable by Kitov (Press release, Kitov Pharmaceuticals , MAR 17, 2020, View Source [SID1234555633]). Each unit contains one American Depositary Shares ("ADS") (or ADS equivalent) and one warrant to purchase one ADS. Each ADS represents one ordinary share, no par value, of Kitov. The ADSs (or ADS equivalents) and warrants included in the units were purchased together in the offering, but were issued separately and are immediately separable. The warrants have an exercise price of $0.325 per ADS and will be exercisable at any time after the date of issuance and will expire five years from the date of issuance.

H.C. Wainwright & Co. acted as the exclusive placement agent for the offering.

Kitov intends to use the net proceeds of this offering to fund the development of its oncology drug candidates, acquisition of new assets and for general working capital purposes.

The offering was made under an effective registration statement on Form F-1 (File No. 333-235729) filed with the Securities and Exchange Commission (the "SEC") and declared effective on March 11, 2020. The offering was made only by means of a prospectus forming part of the effective registration statement. The final terms of the offering are disclosed in a final prospectus filed with the SEC and made available on the SEC’s website at www.sec.gov. Electronic copies of the final prospectus relating to the offering may also be obtained by contacting H.C. Wainwright & Co., 430 Park Avenue, New York, NY 10022, by telephone at (646) 975-6996 or by email at [email protected].

Imfinzi confirmed a sustained overall survival benefit in final analysis of the Phase III CASPIAN trial in 1st-line extensive-stage small cell lung cancer

On March 17, 2020 AstraZeneca reported that High-level results from the final analysis of the Phase III CASPIAN trial showed Imfinzi (durvalumab) in combination with a choice of standard-of-care (SoC) chemotherapies confirmed a sustained, clinically meaningful overall survival (OS) benefit for patients with extensive-stage small cell lung cancer (ES-SCLC) treated in the 1st-line setting (Press release, AstraZeneca, MAR 17, 2020, View Source [SID1234555632]).

In June 2019, the CASPIAN trial met one primary endpoint for Imfinzi plus SoC (etoposide and either carboplatin or cisplatin chemotherapy) by demonstrating a statistically significant and clinically meaningful improvement in OS versus SoC alone at a planned interim analysis.

The second experimental arm testing tremelimumab, an anti-CTLA4 monoclonal antibody, added to Imfinzi and SoC did not meet its primary endpoint of demonstrating a statistically significant improvement in OS in this analysis.

José Baselga, Executive Vice President, Oncology R&D, said: "We are pleased to see the sustained and meaningful survival benefit of Imfinzi for patients with small cell lung cancer after more than two years median follow up. We have already received the first global regulatory approval for Imfinzi with etoposide plus either carboplatin or cisplatin and remain on track for more approvals soon as we provide patients an important new 1st-line treatment option."

The safety and tolerability for Imfinzi and tremelimumab were consistent with the known safety profiles of these medicines. The data will be presented at a forthcoming medical meeting.

Imfinzi in combination with etoposide and either carboplatin or cisplatin is currently under regulatory review for the treatment of ES-SCLC in the 1st-line setting based on the Phase III CASPIAN trial in the US, EU and Japan. The US Food and Drug Administration has granted a Priority Review with a Prescription Drug User Fee Act date set for the first quarter of 2020.

As part of a broad development programme, Imfinzi is also being tested following concurrent chemoradiation therapy in patients with limited-stage SCLC in the Phase III ADRIATIC trial with data anticipated in 2021.

Small cell lung cancer

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% classified as SCLC.2 SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.3,4 About two thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body.5 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.5

CASPIAN

CASPIAN is a randomised, open-label, multi-centre, global, Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation. The trial was conducted in more than 200 centres across 23 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms.

Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the Phase III PACIFIC trial. Imfinzi recently received its first global approval for the 1st-line treatment of ES-SCLC in combination with SoC chemotherapy in Singapore. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumours.

Tremelimumab

Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation, priming the immune response to cancer and fostering cancer cell death. Tremelimumab is being tested in a clinical trial programme in combination with Imfinzi in NSCLC, SCLC, bladder cancer, head and neck cancer and liver cancer.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action. We aim to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with the approved medicines Iressa (gefitinib) and Tagrisso (osimertinib), and its ongoing Phase III trials ADAURA, LAURA, and FLAURA2.6-8 We are also committed to addressing tumour mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD which test Tagrisso in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines. Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate is in development for metastatic non-squamous HER2-overexpressing or HER2-mutated NSCLC including trials in combination with other anticancer treatments.

An extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a targetable genetic mutation which represents up to three-quarters of all patients with lung cancer.9 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON, and PEARL) and for patients in earlier stages of disease including potentially-curative settings (Phase III trials AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in combination with tremelimumab and/or chemotherapy. Imfinzi is also in development in the Phase II combination trials NeoCOAST, COAST and HUDSON in combination with potential new medicines from the early-stage pipeline.

AstraZeneca’s approach to Immuno-Oncology (IO)

Immuno-oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca believes that IO-based therapies offer the potential for life-changing cancer treatments for the clear majority of patients.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca’s Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

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 six new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the 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.