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.

On October 3, 2017 Gilead Sciences, Inc. (Nasdaq: GILD) reported the completion of the previously announced transaction for Dodgers Merger Sub, Inc., a wholly-owned subsidiary of Gilead (“Purchaser”), to acquire Kite Pharma, Inc. (Nasdaq: KITE) for $180 per share, net to the seller in cash, without interest, or approximately $11.9 billion in the aggregate (Press release, Gilead Sciences, OCT 3, 2017, View Source [SID1234520768]).

On August 28, 2017, Gilead and Kite announced that Kite, Gilead and Purchaser had signed a definitive merger agreement pursuant to which a tender offer would be made. Pursuant to the merger agreement, Gilead and Purchaser commenced a tender offer on September 5, 2017 to acquire all outstanding shares of Kite at a price of $180 per share, net to the seller in cash, without interest. On October 3, 2017, Gilead announced that it had successfully completed the tender offer for all outstanding shares of common stock of Kite and had accepted for payment all shares validly tendered and not withdrawn as of the expiration time of the tender offer and would promptly pay for such shares, which shares represented approximately 66.20% of Kite’s outstanding shares (including 2,003,002 shares delivered through Notices of Guaranteed Delivery, representing approximately 3.46% of the shares outstanding). Pursuant to the terms of the merger agreement, Purchaser merged with and into Kite on October 3, 2017. All outstanding shares of common stock of Kite, other than (i) shares owned by Gilead, Purchaser or any of their direct or indirect wholly-owned subsidiaries, (ii) shares owned by Kite (or held in Kite’s treasury) and (iii) shares held by Kite stockholders who properly demand appraisal for their shares under Delaware law, were canceled and converted into the right to receive cash equal to the $180 price per share.

As a result of the completion of the merger, Kite has become a wholly-owned subsidiary of Gilead and the common stock of Kite will no longer be listed for trading on the NASDAQ Global Select Market, which is expected to take effect as of the close of market on October 3, 2017.

“We are excited to welcome more than 700 talented Kite employees to the Gilead organization,” said John F. Milligan, PhD, Gilead’s President and Chief Executive Officer. “Throughout our respective histories, each company has demonstrated a deep commitment to advancing life-saving therapies for people who need them. I look forward to all that we will accomplish together, as a combined organization.”

Bank of America Merrill Lynch, Lazard and Barclays acted as financial advisors to Gilead. Skadden, Arps, Slate, Meagher & Flom LLP acted as Gilead’s legal advisors.

Centerview Partners acted as exclusive financial advisor to Kite. Jeffries LLC and Cowen and Company, LLC also provided advice to Kite. Sullivan & Cromwell LLP and Cooley LLP acted as Kite’s legal advisors.

On October 3, 2017– Seattle Genetics, Inc. (NASDAQ:SGEN) and Takeda Pharmaceutical Company Limited (TSE:4502) reported final data from the ADCETRIS (brentuximab vedotin) pivotal Phase 2 clinical trial in relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) were published in the journal Blood (Press release, Seattle Genetics, OCT 3, 2017, View Source [SID1234520761]). The manuscript, which summarizes the five-year, end-of-study results, highlights durable, long-term remissions in sALCL patients treated with ADCETRIS monotherapy. The manuscript is available online today and will be included in a future print edition of Blood. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of Hodgkin lymphoma cells and several types of non-Hodgkin lymphoma, including sALCL. ADCETRIS is being evaluated globally as the foundation of therapy for CD30-expressing lymphomas in more than 70 corporate- and investigator-sponsored clinical trials.

“Historically, sALCL patients who have recurrent or refractory disease have a poor prognosis and outcome with few effective and durable treatment options,” said Barbara Pro, M.D., Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, and lead author of the Blood manuscript. “Publication of the five-year follow up from the pivotal phase 2 clinical trial results represents a significant milestone for the sALCL community by demonstrating that treatment with single-agent brentuximab vedotin resulted in high response rates and durable, long-term remissions in conjunction with a manageable safety profile.”

“These data from the pivotal trial in sALCL demonstrate the long-term clinical benefit of ADCETRIS in the treatment of this disease, with an estimated five-year survival rate of 60 percent and progression-free survival rate of 39 percent,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “In addition to achieving sustained remissions in the relapsed sALCL treatment setting, these data support the evaluation of ADCETRIS in earlier lines of therapy, including in the ongoing Phase 3 ECHELON-2 clinical trial in frontline mature T-cell lymphoma, also known as peripheral T-cell lymphoma.”

“With the five-year data of ADCETRIS in relapsed or refractory classical Hodgkin lymphoma published in Blood in July 2016, these results in sALCL represent the second CD30-expressing malignancy in which five-year data has confirmed clinically significant durable remissions,” said Jesús Gomez-Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “These findings further substantiate our goal to establish ADCETRIS as the foundation of therapy for CD30-expressing lymphomas.”

The pivotal, single-arm trial, which supported approvals of ADCETRIS by the FDA in 2011 and the European Medicines Agency (EMA) in 2012 for this indication, was conducted in 58 relapsed or refractory sALCL patients to assess the efficacy and safety of single-agent ADCETRIS. After a follow-up period of approximately five years, the final results from the pivotal trial include:

The median overall survival was not yet reached and median progression-free survival was estimated at 20 months (95% confidence interval [CI]: 9.4, -). The estimated five-year overall survival and progression-free survival rates were 60 percent and 39 percent, respectively.
Of the 58 patients treated, 38 patients (66 percent) had a complete remission, with the median response duration not reached. For patients who had a complete remission, the median overall survival and progression-free survival were not yet reached.
Sixteen of the 38 patients (42 percent) who achieved a complete remission continued to be followed and remained in remission for over five years at study closure. Of these patients, eight underwent either autologous or allogenic consolidative stem cell transplants while in remission, and eight received no further therapy.
The most common adverse events of any grade occurring in 20 percent or more of patients were peripheral neuropathy, nausea, fatigue, pyrexia, diarrhea, rash, constipation and neutropenia. Of the 33 patients who experienced peripheral neuropathy, 30 patients (91 percent) experienced complete resolution or some improvement of symptoms at last follow-up.
About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 clinical trials, including four Phase 3 studies: the ECHELON-1 trial in frontline classical Hodgkin lymphoma from which positive top-line results were recently reported, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, the completed ALCANZA trial in cutaneous T-cell lymphoma that supported the supplemental BLA with a Prescription Drug User Fee Act (PDUFA) target action date of December 16, 2017, and the recently initiated CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.