On October 3, 2017 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a pioneer in the discovery and development of CAR-T cell therapies, reported exciting early clinical results of the first dose-level in the hematological arm of its THINK trial (THerapeutic Immunotherapy with CAR-T NKG2D) (Press release, Celyad, OCT 3, 2017, View Source [SID1234520787]).

Christian Homsy, CEO of Celyad comments: “We are pleased to have demonstrated the first objective clinical response of CYAD-01 (a.k.a. CAR-T NKG2D) as this is the very first time a relapsed, refractory AML patient has reached a MLFS with gene-engineered T cells without pre-conditioning lymphodepletion nor additional other concurrent treatment to CYAD-01 administration. This success further reinforces our confidence in our approach and the validity of NKG2D ligands as a target. We will now use the collected data to move forward with the next stage of our product development: reinforcing responses in as many clinical settings as possible.”

At the first dose-level 3×108 CYAD-01 T cells were administered without any prior conditioning chemotherapy to a cohort of three patients with hematologic cancer (two with AML and one with Multiple Myeloma, MM). One AML patient has achieved a MLFS after administration with CYAD-01 at the H. Lee Moffitt Cancer Center and Research Institute (Florida, USA).

Dr. David Sallman, Assistant Member in the Malignant Hematology Department of Moffitt Cancer Center, comments “The results announced today regarding CYAD-01 provide the first clinical validity of CYAD-01 as a tumor-specific antigen-receptor and AML as a disease sensitive to gene-engineered cell therapies. As antigen targeting offers significant challenges in AML, this outcome brings hope for the further use of gene-engineered T cells for patients with AML that have run out of therapeutic options. It’s all the more striking that this outcome was observed without any prior lymphodepletion highlighting the potential of using a physiologic antigen-receptor.”
AML is a blood cancer characterized by a rapid increase of abnormal white blood cells in the bone marrow, which in turn affects the production of normal blood cells. More than

• 1 MLFS for Morphological Leukemia-Free Status

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20,000 people in the US and almost as many people in Europe are diagnosed every year with this type of blood cancer. As AML’s incidence increases with age and as population ages, it is expected that a growing number of people might be affected by this type of cancer.

Dr. Frédéric Lehmann, Vice President Clinical Development and Medical Affairs at Celyad adds: “With this first objective and ongoing response, obtained without additional treatments such as lymphodepletion, CYAD-01 confirms the potential to treat relapsed refractory AML, one of the deadliest cancers with a median overall survival of less than 4 months. The concept of CAR-T cells with the NKG2D receptor is now progressing to further validation.”
The THINK trial, conducted in the US and in Europe, includes two stages: a dose escalation and an extension stage. The dose escalation is being conducted in parallel in solid cancers (colorectal, pancreatic, ovarian, triple negative breast and bladder) and in hematologic (AML and MM) cancer groups, while the extension phase will evaluate in parallel each tumor type independently. The dose escalation design includes three dose levels adjusted to body weight: up to 3×108, 1×109 and 3×109 CYAD-01. At each dose, the patients receive three successive administrations, two weeks apart, of CYAD-01 at the specified dose. To date, 14 patients have been dosed in the THINK trial. One Grade Three and one Grade Four event have been observed, both resolved within 72 hours. No dose limiting toxicities (DLT) nor deaths related to the investigational product have been reported.
Celyad’s management will host a conference call at 2pm CEST/8am EDT on Friday October 6, 2017

Conference Call Details

A conference call will be held on Friday October 6, 2017 at 2:00pm (CEST) / 8:00am (EDT) to provide an update on Celyad’s clinical strategy. Christian Homsy, Chief Executive Officer, and Patrick Jeanmart, Chief Financial Officer, will deliver a brief presentation followed by a Q&A session.

Participants are asked to call the assigned numbers approximately five minutes before the conference call begins.
The call can be accessed by dialling the numbers below and using the passcode: 95148855

International: +44 (0) 2071 928338
Belgium: 02 793 3847
France: 0170700781
UK: 0800 2796619
US: 1 877 8709135

On October 3, 2017 Siamab Therapeutics, Inc., a biopharmaceutical company developing novel cancer immunotherapies, reported the presentation of new preclinical data for its novel anti-Sialyl-Tn (STn) antibodies and antibody drug conjugates (ADCs) that show inhibition of tumor progression in in vivo and in vitro patient derived xenograft (PDX) ovarian cancer models with complete regression in some treatment arms (Press release, Siamab Therapeutics, OCT 3, 2017, View Source [SID1234520772]). The data were presented in a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Addressing Critical Questions in Ovarian Cancer Research and Treatment Meeting, held October 1-4, 2017 in Pittsburgh, Pennsylvania. ST1, Siamab’s lead antibody program targeting STn, is in late stage preclinical development for the treatment of solid tumors.

Siamab is developing monoclonal antibody (mAb) therapeutics that target cancer cell surface glycans called tumor-associated carbohydrate antigens (TACAs), a novel class of cancer-specific antigens found on the cell surface of many solid tumors. TACAs are implicated in immune suppression, chemoresistance, and a cancer stem cell (CSC) phenotype. The elevated presence of STn, a key TACA observed in the majority of ovarian tumors, is associated with metastatic disease, poor prognosis, and reduced overall survival. Elevation of STn expression is linked to chemotherapy resistance and enables tumors to evade the host immune system. Siamab has also identified the presence of STn on myeloid-derived suppressor cells, which are major regulators of immune response in cancer and influence the tumor microenvironment by suppressing T cells. STn is a major reported constituent of two established CSC biomarkers, CD44 and MUC1, which reside on both CSCs and mature malignant cells in some cancer types.

In the poster presentation, titled Targeting the Tumor-Associated Carbohydrate Antigen STn with Humanized anti-Sialyl-Tn Monoclonal Antibody-drug Conjugates Inhibits Ovarian Cancer Tumor Growth in vitro and in vivo,” Siamab scientists and collaborators reported data demonstrating anti-tumor effect in vitro utilizing humanized anti-STn ADCs as well as inhibition of tumor progression in vivo in both cell line- and PDX ovarian cancer models with complete regressions observed in some treatment groups. In a chemo-naïve ovarian PDX model, 75% of animals given ST1 are completely tumor free at 52 days post treatment as compared to control-treated animals. In a chemoresistant ovarian PDX model, tumors regressed by more than 50% in 75% of the animals in the ST1 group as compared to control-treated animals. No significant weight loss was observed for any of the treatment groups, indicating the therapy was well tolerated by all the groups. A decrease in STn expression was noted in the tumors following treatment, indicating that Siamab’s anti-STn ADC was depleting the mAb-targeted STn+ tumor cells. In addition, researchers utilized the STn-selective antibodies to develop both tissue- and serum-based biomarker assays with the potential to become companion diagnostics.

“Our research findings show that tumor-associated carbohydrate antigens, and in particular STn, have the potential to offer a unique approach to targeting cancer cells,” said Jeff Behrens, president and chief executive officer of Siamab. “STn is not only an intriguing cancer biomarker and therapeutic target, but

manipulating STn biology offers the potential to have significant immune re-engagement and anti-metastatic therapeutic benefits. These data demonstrate that high-affinity, STn-selective humanized mAbs show promise as therapies for ovarian tumors, as well as tools for patient stratification and pharmacodynamic biomarker assessments.”

Ovarian cancer is the leading cause of death from gynecological malignancies in the United States. The current standard of care is tumor debulking followed by chemotherapy. This treatment results in approximately 70% of patients achieving an initial complete clinical response. However, many of these patients will unfortunately relapse with chemoresistant disease developing in part due to the presence of CSCs within the tumor. Ovarian CSCs have been shown to be resistant to chemo- and radiotherapy.

On October 3, 2017 Sir Harpal Kumar, Chief Executive of Cancer Research UK, reported that, after more than 10 years leading the charity, he plans to conclude his role in the spring of 2018 (Press release, Cancer Research UK, OCT 3, 2017, View Source [SID1234520770]).

Aside from overseeing significant growth in income and research investment, Sir Harpal successfully led the Independent NHS Cancer Taskforce for England and Cancer Research UK’s major contribution to the development of the Francis Crick Institute. As well as the progress that has been made in UK cancer survival rates over the last 10 years, under his leadership Cancer Research UK has made significant strides forward in the fields of cancer prevention and early diagnosis.

Sir Harpal, who has worked for the charity for 15 years in total, was awarded a knighthood in the 2016 New Year’s Honours in recognition for all that he has done in the fight against cancer.

Sir Harpal said: “My passion and excitement for Cancer Research UK’s work is as high as it has ever been. But I have always believed that organisations benefit from refreshed leadership every so often and Cancer Research UK is no exception. Our progress is accelerating, and patients and the public are realising the benefit of our work in ever greater numbers.

“I am deeply grateful to every volunteer, scientist, member of staff and supporter for the outstanding contributions they have made since I’ve been Chief Executive. I look forward to using my remaining time with the organisation to continue to advance our critically important mission.”

Professor Sir Leszek Borysiewicz, Chairman of Cancer Research UK, said: “I would like to thank Harpal for his tremendous contribution to the charity over the last 15 years. Cancer Research UK is a truly remarkable organisation and even more so because of Harpal’s inspirational leadership. I am delighted that Harpal has agreed to stay on until the spring and we have commenced a search for his replacement. We anticipate being able to make an appointment to coincide with Harpal’s departure and plan for a smooth transfer.”

On October 3, 2017 Amgen (NASDAQ:AMGN) and CytomX Therapeutics, Inc., (NASDAQ:CTMX) reported that the companies have entered into a strategic collaboration in immuno-oncology (Press release, Amgen, OCT 3, 2017, View Source [SID1234520769]). The companies will co-develop a CytomX Probody T-cell engaging bispecific against the Epidermal Growth Factor Receptor (EGFR), a highly validated oncology target expressed on multiple human cancer types. Probody T-cell engaging bispecifics are antibody constructs capable of directing cytotoxic T-cells in tumor microenvironments. In preclinical studies, CytomX’s Probody versions of EGFRxCD3 bispecific therapeutics induced tumor regressions and increased the therapeutic window for this high potential cancer target.

“Our collaboration with CytomX leverages Amgen’s development leadership in bispecifics and expands our immuno-oncology capabilities with an additional and complementary bispecific technology,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “EGFR is a particularly compelling target on which to employ the CytomX Probody platform given its potential to localize activity within tumors while limiting potential toxicity.”

“Probody-based T-cell engaging bispecific antibodies offer significant potential in treating cancers by employing localized therapeutic activity within tumor tissue,” said Sean McCarthy, D.Phil., president and chief executive officer of CytomX Therapeutics. “Through this collaboration, we are positioned to combine Amgen’s industry-leading expertise in leveraging bispecifics to activate a patient’s immune-system with CytomX’s ability to design potent new therapies that exploit unique conditions in the tumor microenvironment. Development of Probody-based T-cell engaging bispecifics further validates the broad applicability of the Probody platform in addressing unmet needs in oncology.”

Under the terms of the agreement, Amgen and CytomX will co-develop a Probody T-cell engaging bispecific against EGFRxCD3 with CytomX leading early development. Amgen will lead later development and commercialization with global late-stage development costs shared between the two companies. Amgen will make an upfront payment of $40 million and purchase $20 million of CytomX common stock. CytomX will be eligible to receive up to $455 million in development, regulatory and commercial milestones for the EGFR program. Amgen will lead global commercial activities with CytomX able to opt into a profit share in the U.S. and receive tiered, double-digit royalties on net product sales outside of the U.S.

Amgen will also receive exclusive worldwide rights to develop and commercialize up to three additional, undisclosed targets. Should Amgen ultimately pursue all of these targets, CytomX will be eligible to receive up to $950 million in additional upfront and milestone payments and high single-digit to mid-double digit royalty payments on any resulting products. CytomX will also receive the rights from Amgen to an undisclosed preclinical T-cell engaging bispecific program; Amgen is eligible to receive milestones and royalty payments on any resulting products from this CytomX program.