Spectrum Pharmaceuticals Highlights Three Posters at the 60th Annual Meeting of the American Society of Hematology

On November 30, 2018 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, reported presentations of clinical and scientific data related to Peripheral T-cell Lymphoma (PTCL) and EVOMELA (melphalan) at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) being held in San Diego, California, from December 1-4, 2018 (Press release, Spectrum Pharmaceuticals, NOV 30, 2018, View Source [SID1234531743]).

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For more information about the ASH (Free ASH Whitepaper) annual meeting and for a complete list of abstracts, please refer to the conference website at View Source

The following posters will be presented at the ASH (Free ASH Whitepaper) meeting:

Management of Mucositis with Use of Leucovorin as Adjunct to Pralatrexate in Treatment of Patients with Hematological Malignancies including of Peripheral and Cutaneous T-Cell Lymphomas-Results from a Prospective Multicenter Phase 2 Clinical Trial. Poster 2910; Presented on Sunday, Dec 2, 6:00 PM-8:00 PM, Hall GH
Role of Single Agent and Combination Chemotherapy Strategies in Relapsed/Refractory Peripheral T-Cell Lymphoma: Results from the Complete Registry. Poster 2926; Presented on Sunday, Dec 2, 6:00 PM-8:00 PM, Hall GH
Safety and Efficacy of Evomela in Myeloma Autotransplants; Poster 3446; Presented on Sunday, Dec 2, 6:00 PM-8:00 PM, Hall GH

The Leukemia & Lymphoma Society® Releases Results of its Precision Medicine Trial in Deadly Leukemia at American Society of Hematology Annual Meeting

On November 30, 2018 The Leukemia & Lymphoma Society (LLS) reported it continues to deliver on its promise to "Beat AML," the deadliest of the blood cancers, through its groundbreaking Beat AML Master Clinical Trial, a precision medicine approach to treating these cancer patients (Press release, The Leukemia & Lymphoma Society, NOV 30, 2018, View Source;lymphoma-society-releases-results-of-its-precision-medicine-trial-in-deadly-leukemia-at-american-society-of-hematology-annual-meeting-300758232.html [SID1234531760]).

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The first results of this trial, to be announced Sunday and Monday at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, validate the feasibility of using genomic sequencing to identify the patients’ specific type of acute myeloid leukemia (AML) and give them a targeted treatment within seven days, a first-ever approach to this disease, which, until recently, had not seen treatment advances in 40 years.

As the world’s largest nonprofit dedicated to fighting blood cancers, LLS is uniquely qualified to drive the Beat AML Master Clinical Trial, an unprecedented collaboration that aims to change the paradigm of treatment through a precision medicine approach. LLS has united prominent scientists at top cancer centers, multiple pharmaceutical companies, several technology companies and the U.S. Food and Drug Administration (FDA) to bring new and better treatments to AML patients in urgent need. LLS is the first nonprofit health organization to sponsor a cancer clinical trial.

Five Beat AML Master Clinical Trial abstracts to be presented at 60th Annual ASH (Free ASH Whitepaper) Meeting:

"Initial Report of the Beat AML Umbrella Study for Previously Untreated AML: Evidence of Feasibility and Early Success in Molecularly Driven Phase 1 and 2 Studies [Abstract #559], at press briefing Sunday, December 2 at 8 a.m. PT, and in an oral scientific session on Monday, December 3 at 7 a.m.

Additional progress on Beat AML will be presented in abstracts 287, 1489, 2773, and 4053

According to Brian Druker, MD, director of OHSU Knight Cancer Institute, and a co-lead investigator for LLS’s Beat AML Master Clinical Trial, "For four decades, AML patients have been treated with a one-size-fits all approach, with most receiving a standard chemotherapy combination almost immediately upon diagnosis. But many older adults cannot tolerate the toxicity. With LLS’s vision and support, we’ve been able to bring a cutting edge medical approach to developing better treatments faster and helping more patients. With the Beat AML trial we’re doing a better job of matching patients to therapies."

More than 20,000 Americans are diagnosed with AML and 10,000 die from the cancer annually. The five-year-survival rate for older adults remains dismal at less than 20 percent.

The study, two years underway, has already shown that patients diagnosed with AML, a complex disease with multiple subtypes, benefit from having their specific genetic subtype identified quickly before receiving traditional treatment, so they can receive a targeted therapy that matches their individual cancer-driving genetic mutations. The trial has now screened more than 400 patients at 13 clinical centers across the U.S., with patients entering the trial receiving one of seven investigational therapies.

The impact of the Beat AML initiative and progress in AML in general was addressed last night at an LLS roundtable event, Innovation in Research: Blood Cancers and Beyond, moderated by NBC News Medical Correspondent John Torres, MD, and veteran healthcare journalist Ron Winslow. Advancements in immunotherapy, genomics and personalized medicine and how they are transforming cancer treatment were all part of the discussion.

LLS president and chief executive officer, Louis J. DeGennaro, PhD, set the stage for the roomful of attending researchers, treating physicians, industry executives and regulators at the Hilton Bayfront San Diego.

"AML is a formidable adversary in the medical and scientific community; this rapidly progressing disease remains one of the most lethal blood cancers," DeGennaro said. "LLS, along with our partners and the FDA, are changing the paradigm for cancer clinical trials, so we can get the right drug to the right patient at the right time."

LLS’s commitment to fighting AML will be among the news headlines of the ASH (Free ASH Whitepaper) conference, highlighted through the significant data being presented in five Beat AML abstracts. Further, LLS’s impact on AML extends beyond the clinical trial. LLS and its collaborators at Johns Hopkins University are also releasing data at the ASH (Free ASH Whitepaper) meeting through several abstracts on AML patient preferences for treatment outcomes, their worries, and their reported side effects from treatment.

According to Amy Burd, PhD, LLS vice president of research strategy and the organization’s lead for the Beat AML initiative, "Taken together, these five Beat AML abstracts tell a story of how, through collaboration, we have put in motion a dynamic trial model that is already having an impact on patients and how doctors approach treatment of AML."

More Progress in AML

Breakthroughs in AML have occurred rapidly over the past two years after a 40-year drought. From the start of 2017 to date, nine AML therapies have received approval from the U.S. Food and Drug Administration (FDA). All have been advanced with LLS support.

Three just received approval this month:

gilteritinib (XOSPATA), developed by Astellas Pharma, received FDA approval on November 28, to treat relapsed and refractory AML patients with a genetic mutation called FLT3, which are seen in approximately one-third of patients with AML. It is the second FLT3 inhibitor to receive FDA approval since 2017; the other, midostaurin (Rydapt ), was approved in April 2017, for newly diagnosed FLT3 AML patients. Gilteritinib is also part of the Beat AML Master Clinical Trial. While this recent approval is for patients who have failed previous treatments, it is being tested in Beat AML as a frontline treatment. Another FLT3 inhibitor, quizartinib is under review with a decision anticipated by Spring.
venetoclax (Venclexta ), developed by Abbvie and Genentech, received approval on November 21, in combination with a chemotherapy – azacitidine, decitabine or low-dose cytarabine (LDAC), in newly diagnosed patients who are aged 75 years and older or are ineligible for intensive chemotherapy due to coexisting medical conditions. This therapy targets the cellular pathway that regulates natural cell death. When this process goes awry as it often does in cancer the body is unable to rid itself of unhealthy cells.
glasdegib (Daurismo ), was also FDA approved on Nov. 21. Pfizer’s AML drug targets a cell signaling pathway called Hedgehog, which is critical for the development of immature cells into cells with more specialized functions. It is approved for patients who are age 75 or older, or who have other chronic health conditions or diseases that might preclude the use of intensive chemotherapy.
One of last night’s panelists, Erkut Bahceci, M.D., vice president, medical sciences-hematology, Astellas Pharma, discussed the approval of gilteritinib.

"We have learned from past failures of prior drugs targeting this same mutation and designed this drug to help overcome those weaknesses," Bahceci said. "In collaboration with the FDA, we were able to speed innovation and achieve this approval quickly. It only took five years since the first patient was treated with gilteritinib."

Other AML therapies approved in 2017 and 2018 are: midostaurin (Rydapt ); enasidenib (Idhifa);(CPX-351) (Vyxeos ); gentuzumab ozogamicin (Mylotarg); arsenic trioxide (Trisenox ); ivosedinib (Tibsovo). LLS supported research for each of these therapies.

LLS’s Commitment to AML

LLS has long been committed to leading the offensive on AML, with more than one-quarter of our research budget dedicated to finding new and better treatments. And we continue to provide lifesaving support and advocacy for AML patients and their caregivers. Among our most recent round of grants are multiple projects targeting AML, including a Specialized Center of Research grant led by Craig Jordan, Ph.D., University of Colorado, and his colleagues who are taking a multi-pronged approach to eradicate cancer stem cells in AML patients. The team was pivotal in demonstrating that the aforementioned, recently approved venetoclax can produce long-term disease control in patients with AML, and appears to be a game-changer for the future therapy of this and other diseases.

John Byrd, M.D., of The Ohio State University Comprehensive Cancer Center, and a co-lead investigator of the Beat AML trial, commented that with so many new options now for AML the key will be finding the right combinations.

"If you think of a cake and you only have flour and maybe a little sugar you won’t be able to make a very good cake," Byrd said. "I think now for subsets of AML we probably have the right ingredients to completely change the natural history of this disease. We just need to come up with the recipe for how to combine things."

AVID200, a novel TGF-beta 1 & 3 inhibitor and Potential New Treatment for Myelofibrosis, Featured in a Poster Presentation at the 60th ASH Annual Meeting

On November 30, 2018 Forbius, a clinical-stage company developing biologics for the treatment of cancer and fibrosis, reported that its collaborators at the Icahn School of Medicine at Mount Sinai will present a poster tomorrow, Dec. 1, featuring AVID200, at the 60th ASH (Free ASH Whitepaper) Annual Meeting (Press release, Forbius, NOV 30, 2018, View Source [SID1234531778]).

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Previous studies have shown that hyperactive TGF-beta signaling is a fundamental defect driving bone marrow fibrosis (Chagraoui et al., Blood, 2002). This presentation highlights the ability of AVID200 to shut down TGF-beta signaling, which decreases proliferation of mesenchymal stem cells and their collagen production. Importantly, when cells from myelofibrosis patients were treated with AVID200, this promoted proliferation of normal hematopoietic progenitors, while decreasing the proportion of myelofibrosis malignant progenitor cells.

AVID200 is uniquely positioned to be an effective treatment of MF because of isoform selectivity. TGF-beta 2 has been shown to be a positive promoter of hematopoiesis as well as normal cardiac function, whereas TGF-beta 1 and 3 promote fibrosis and myeloproliferation. AVID200 was therefore designed to selectively neutralize TGF-beta 1 & 3 for optimal efficacy and safety.

A Phase 1 trial evaluating AVID200 in patients with myelofibrosis is planned for early 2019.

The poster, entitled AVID200, a Potent Trap for TGF-β Ligands Inhibits TGF-β 1 Signaling in Human Myelofibrosis, will be presented by Lilian Varricchio, PhD, on Saturday, December 1st from 6:15 PM-8:15 PM PST in Hall GH of the San Diego Convention Center.

The abstract and full details for the poster presentation can be found on the ASH (Free ASH Whitepaper) website.

About AVID200
Forbius developed AVID200 to be a highly potent and isoform-selective TGF-β inhibitor. AVID200 neutralizes TGF-beta 1 and 3 with pM potency. These isoforms are known to be drivers of fibrosis and tumor immune resistance. In contrast, TGF-beta 2 is a positive regulator of hematopoiesis and normal cardiac function, therefore blockade of TGF-beta 2 is undesirable. The ability of AVID200 to selectively target TGF-beta 1 and 3 positions it to be an effective and well-tolerated therapeutic in fibrotic diseases and immune oncology.

Calithera Biosciences to Participate in the 2018 Citi Global Healthcare Conference

On November 30, 2019 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported its participation at the 2018 Citi Global Healthcare Conference (Press release, Calithera Biosciences, NOV 30, 2018, View Source [SID1234535232]). Calithera will host meetings with investors at the conference in New York on Thursday, December 6, 2018.

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Celyad Doses First mCRC Patient in the Phase 1 alloSHRINK Trial Evaluating Non-Gene Edited Allogeneic CAR-T Candidate, CYAD-101

On November 30, 2018 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, reported the injection of the first patient in the Phase 1 alloSHRINK trial evaluating the Company’s non-gene edited allogeneic CAR-T therapy, CYAD-101, administered concurrently with FOLFOX chemotherapy in the treatment of patients with unresectable metastatic colorectal cancer (mCRC) (Press release, Celyad, NOV 30, 2018, View Source [SID1234531747]).

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"The initiation of the alloSHRINK trial marks a critical milestone for our organization," said Dr. Christian Homsy, CEO of Celyad. "CYAD-101 represents a potential first-in-class approach to allogeneic CAR-T therapy and continues to build up Celyad’s leadership position in the allogeneic field, which is anchored by the Company’s robust allogeneic patent estate in the United States and complemented by our novel shRNA-based non-gene edited platform."

Dr. Frédéric Lehmann, VP of Clinical Development & Medical Affairs at Celyad, commented, "CYAD-101 represents Celyad’s second oncology program to enter the clinic for the treatment of metastatic colorectal cancer and balances the Company’s autologous clinical candidate CYAD-01, which has demonstrated encouraging preliminary results in the Phase 1 SHRINK trial. We believe investigating CYAD-101 in the alloSHRINK trial will leverage our clinical experience to date in the treatment of metastatic colorectal cancer as we look to develop novel therapies for this devastating disease."

Celyad also announced that ONO Pharmaceutical Co., Ltd. has given notice to the Company that it will no longer pursue development of CYAD-101 in Japan, Korea and Taiwan. Celyad and ONO Pharmaceutical entered into an exclusive license agreement for the development and commercialization of CYAD-101 in these specified territories in July 2016. Based on the agreement, ONO Pharmaceutical was required to exercise an option following the initiation of the Phase 1 trial for CYAD-101. The agreement has now expired and Celyad controls worldwide development and commercialization rights to CYAD-101.

Press Release

30 November 2018

07:00 am CET

CYAD-101 and alloSHRINK Trial Design

CYAD-101 is an investigational, non-gene edited, allogeneic (donor derived) CAR-T therapy that co-expresses the chimeric antigen receptor NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands expressed on tumor cells and the novel inhibitory peptide TIM (T cell receptor [TCR] Inhibiting Molecule). TCR signaling is responsible for Graft versus Host Disease (GvHD). The expression of TIM reduces signaling of the TCR complex and could therefore reduce or eliminate GvHD in patients treated with CYAD-101.

The alloSHRINK trial (NCT03692429) is an open-label, dose-escalation trial that will assess the safety and clinical activity of CYAD-101 administered concurrently with FOLFOX chemotherapy in patients with unresectable mCRC. Patients will receive six cycles of FOLFOX chemotherapy every two weeks and three administrations of CYAD-101 every two weeks 48 hours after the initiation of chemotherapy cycles one, two and three. The three dose levels to be evaluated are 100 million, 300 million and 1 billion cells per injection, respectively.