On February 27, 2019 ALX Oncology, a clinical-stage immuno-oncology company developing therapies to block the CD47 checkpoint mechanism, reported that preclinical data for its SIRPα antibody research program will be presented at the 2019 Keystone Symposia Conference (Keystone), Cancer Immunotherapy in Whistler, British Columbia and the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, Georgia (Press release, ALX Oncology, FEB 27, 2019, View Source [SID1234533751]).

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CD47/SIRPα interaction is a key checkpoint mechanism exploited by cancer cells to escape immunological surveillance. While CD47 is widely expressed in human cells, SIRPα, the CD47 inhibitory receptor, is mainly expressed in myeloid cells and neurons. ALX148, a CD47 blocker with an inactive Fc domain, is generally well tolerated and demonstrates anti-cancer activity in combination with trastuzumab and pembrolizumab in patients with anti-HER2 and checkpoint inhibitor resistant/refractory disease (SITC 2018, P335). Another approach to block this interaction is to target SIRPα.

"Targeting the CD47/SIRPα pathway is an exciting new approach that shows promise in clinical trials. By targeting SIRPα, we can investigate the similarities and differences of an orthogonal strategy to inhibit this axis," said Hong Wan, Ph.D., ALX Oncology’s Chief Scientific Officer. "Our panel of proprietary high affinity monoclonal antibodies provides diverse epitope coverage across the extracellular surface of SIRPα. These antibodies are cross-reactive to human, monkey and rodent SIRPα variants, which enables robust clinical translation. Importantly, these antibodies bind to all human SIRPα variants, a critical attribute for a global patient population."

ALX Oncology’s SIRPα antibodies enhance the antitumor activity of immune checkpoint inhibitors, with reduction of metastases, eradication of tumors, and acquisition of memory immune response in tumor-bearing mice with intact immune systems. The cellular immune response in syngeneic models shows that these SIRPα antibodies enhance innate and adaptive anti-cancer immunity, providing a rationale for combination with other immunotherapies. In an exploratory toxicology study in monkeys, the selected SIRPα antibodies demonstrate a favorable pharmacokinetic, target occupancy and tolerability profile.

Together, these preclinical data provide a compelling rationale to advance the development of anti-SIRPα therapy for patients with cancer.

Keystone Presentation Information
Title: Discovery of monoclonal antibodies targeting myeloid checkpoint SIRPα to enhance anti-tumor immunity
Session: Poster session 3
Session Date: Wednesday, March 13, 2019
Location: Whistler Conference Centre
Poster Number: 3022

AACR Presentation Information
Title: Antibodies to SIRPα enhance innate and adaptive immune responses to promote anti-tumor activity
Session Category: Immunology
Session Title: Therapeutic Antibodies 1
Session Date and Time: Sunday, March 31, 2019 1:00 PM – 5:00 PM ET
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 23
Abstract Number: 562

On february 27, 2019 Tetraphase Pharmaceuticals, Inc. (NASDAQ:TTPH), a biopharmaceutical company focused on developing and commercializing novel tetracyclines to treat life-threatening conditions, reported it will present three posters on TP-2846, the Company’s newly revealed pipeline candidate for acute myeloid leukemia (AML) (Press release, Tetraphase Pharmaceuticals, FEB 27, 2019, View Source [SID1234533750]). The posters will be presented at the 2019 American Association for Clinical Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place March 29 – April 3 at the Georgia World Congress Center in Atlanta. The poster presentations will include in vitro and in vivo data supporting TP-2846’s potential as a novel tetracycline antileukemia agent.

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"Decades of research have shown that tetracyclines hold potential as anticancer agents, but to date, optimizing a tetracycline for oncology has proven elusive," said Guy Macdonald, President and Chief Executive Officer. "Leveraging our proprietary and productive discovery platform, we identified TP-2846, a structurally diverse tetracycline and potential new antileukemia agent with potent in vitro and in vivo activity. We look forward to further discussing the potential of TP-2846 at AACR (Free AACR Whitepaper) and building on this encouraging preclinical dataset."

"TP-2846 represents a new mechanism of action with potential application for AML patients regardless of mutation status," said Jacques Dumas, Ph.D., Chief Scientific Officer. "By using our fully synthetic technology for building tetracyclines, we have been able to optimize TP-2846 for AML, warranting its further study in this patient population."

The details for the data presentations at AACR (Free AACR Whitepaper) are as follows:

Abstract Number: 3857
Title: Discovery and structure-activity relationship studies of TP-2846: a novel tetracycline antileukemia agent
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 2
Session Date and Time: Tuesday, April 2, 2019 from 1:00 PM – 5:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 12

Abstract Number: 3880
Title: In vivo activities of TP-2846: a novel tetracycline antileukemia agent
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 2
Session Date and Time: Tuesday, April 2, 2019 from 1:00 PM – 5:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 12

Abstract Number: 4802
Title: In vitro characterization of TP-2846: a novel tetracycline antileukemia agent
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 3
Session Date and Time: Wednesday, April 3, 2019 from 8:00 AM – 12:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 13

On February 27, 2019 Cullinan Oncology is reported that its co-founder and Chief Scientific Officer, Biologics, Patrick Baeuerle, has been honored by the European Molecular Biology Laboratory (EMBL) (Press release, Cullinan Oncology, FEB 27, 2019, View Source [SID1234533749]). The EMBL has presented Baeuerle with the 2019 Lennart Philipson Award for his pivotal role in developing cancer immunotherapies.

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The award focuses on Baeuerle’s many contributions to the field of immuno-oncology, including his efforts at Micromet and subsequently Amgen where he developed bispecific antibodies known as BiTEs (Bispecific T cell Engagers). BiTEs engage the body’s T cells to facilitate the destruction of cancer cells. Baeuerle led the development of Blincyto, the first bispecific antibody approved by the FDA, for relapsed/refractory acute lymphoblastic leukemia (ALL).

"Patrick’s contributions to the fight against cancer have been significant and this recognition is well deserved. We are fortunate to have his knowledge, expertise, and leadership at Cullinan as we work to develop the next breakthroughs for patients," said Owen Hughes, CEO at Cullinan Oncology.

In addition to his role at Cullinan, Patrick Baeuerle is an Executive Partner at MPM Capital. He is also the founder of MPM-funded cancer immunotherapy companies Harpoon Therapeutics (NASDAQ: HARP), TCR2 Therapeutics (NASDAQ GS: TCRR), iOmx Therapeutics, and Maverick Therapeutics.

To access the EMBL announcement click here.

About the Lennart Philipson Award

The Lennart Philipson Award (LPA) was created to honor EMBL’s second Director General, Lennart Philipson (1982-1993). The Award recognizes outstanding and validated contributions in translational research in human health and/or technology innovation in the life sciences.

On February 27, 2019 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer, autoimmune/inflammatory, and other diseases, reported the company will participate in two upcoming investor conferences in March (Press release, Alpine Immune Sciences, FEB 27, 2019, View Source [SID1234533748]).

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Cowen and Company 39th Annual Health Care Conference
Date: Tuesday, March 12, 2019
Time: 9:20 a.m. Eastern Time
Location: Boston, MA

Oppenheimer 29th Annual Healthcare Conference – Analyst-Led Fireside Chat
Date: Tuesday, March 19, 2019
Time: 1:35 p.m. Eastern Time
Location: New York, NY

A live webcast of each presentation will be available online in the investor relations section of the company’s website at View Source A replay of the presentations will be available on the company website for 90 days following the webcast.

On February 27, 2019 Orion Corporation and Bayer reported the completion of the rolling submission of a New Drug Application (NDA) for darolutamide to the U.S. Food and Drug Administration (FDA) (Press release, Bayer, FEB 27, 2019, View Source [SID1234533747]).

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The submission, which was initiated in December 2018, is based on data from the Phase III ARAMIS trial in men with non-metastatic castration-resistant prostate cancer (nmCRPC) showing a statistically significant improvement in metastasis-free survival (MFS) for darolutamide plus androgen deprivation therapy (ADT). Darolutamide plus ADT has shown a favorable safety profile compared to placebo plus ADT.1 These data were recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in San Francisco and published simultaneously in The New England Journal of Medicine.

"Darolutamide is highly effective in the patient population with non-metastatic castration-resistant prostate cancer, and it has a side-effect profile that parallels that of placebo. Patients who received Darolutamide had substantially longer MFS in the ARAMIS trial, and there was also a strong trend for improved overall survival. These results are truly exciting. We are looking forward to taking the next steps in bringing Darolutamide to men with nmCRPC and their treating physicians", said Christer Nordstedt, MD, PhD, Senior Vice President, Research and Development, Orion Corporation.

Bayer has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for darolutamide in men with nmCRPC. Bayer is also in discussions with other health authorities regarding a submission of darolutamide. The compound is being developed jointly by Orion Corporation and Bayer.

About ARAMIS

The ARAMIS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral darolutamide in patients with nmCRPC who are currently being treated with ADT and are at high risk for developing metastatic disease. 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide twice a day or placebo along with ADT.

About darolutamide

Darolutamide is a non-steroidal androgen receptor antagonist with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. In preclinical studies, darolutamide demonstrated lower blood-brain barrier penetration compared to other currently available AR antagonists. This may also explain the overall low incidence of central nervous system (CNS)-related adverse events seen in the ARAMIS Phase III study.

In addition to the Phase III trial ARAMIS in men with nmCRPC, darolutamide is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS). Information about these trials can be found at www.clinicaltrials.gov.

Darolutamide is not approved by the U.S. FDA, the European Medicines Agency or any other health authority.

About castration-resistant prostate cancer (CRPC)

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.2 In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.2 Prostate cancer is the fifth leading cause of death from cancer in men.2 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system.3 It mainly affects men over the age of 50, and the risk increases with age.4 Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location.5 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.6

CRPC is an advanced form of the disease where the cancer keeps progressing even when the amount of testosterone is reduced to very low levels in the body. The field of treatment options for castration-resistant patients is evolving rapidly, but until recently, there have been no effective treatment options for CRPC patients who have rising prostate-specific antigen (PSA) levels while on ADT and no detectable metastases. In men with progressive nmCRPC, a short PSA doubling time has been consistently associated with reduced time to first metastasis and death.7