On December 3, 2018 TRIGR Therapeutics, Inc. ("TRIGR"), and ABL Bio, Inc. ("ABL"), reported that they have entered into a collaboration and license agreement for TR009 (formerly known as ABL001 or NOV1501), an ABL developed bispecific antibody candidate targeting two important angiogenic factors, VEGF and DLL4 (Press release, TRIGR Therapeutics, DEC 3, 2018, View Source [SID1234531844]). The license agreement is exclusive and global, excluding the Republic of Korea for all oncology indications and excluding the Republic of Korea and Japan for all ophthalmology indications. This agreement is in addition to the recently announced agreement whereby TRIGR licensed pre-clinical immune engaging bispecific antibodies from ABL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

TR009 is currently in a dose escalation Phase 1a study being conducted at the Samsung Medical Center in South Korea. The phase 1a study is sponsored by ABL and National OncoVenture (NOV), a South Korean government funded oncology drug development program. A phase 1b study looking to combine TR009 with chemotherapy and a checkpoint inhibitor is expected to commence in the latter part of 2019.

To date, 12 patients have been dosed with TR009 and no dose-limiting toxicities (DLTs) have been reported. Based on preliminary patient data, TR009 single agent clinical activity has been demonstrated across all dose levels among heavily pre-treated (5+ lines of prior therapy) cancer patients with solid tumors including gastric, colon, GIST, and ovarian cancers. At the mid-dose level cohort, more than half of the patients have experienced durable clinical benefit in terms of tumor stabilization (stable disease).

Under the terms of the agreement, TRIGR is responsible for global Phase 2 and subsequent clinical development and commercialization activities for TR009 for all oncology indications. ABL will receive an upfront payment of $5 million and is eligible to receive up to $405 million in regulatory and sales milestones and royalties on oncology sales of TR009 outside of the Republic of Korea. For ophthalmology indications, TRIGR is responsible for all development and commercialization within its territories. ABL is eligible to receive up to $185 million in milestone payments and royalties on TR009 ophthalmology sales outside of the Republic of Korea and Japan.

"We are delighted to expand our relationship with ABL," said George Uy, CEO of TRIGR. "Combining both companies’ core competencies and resources will optimize our chances of success in developing this novel cancer therapy. ABL has an outstanding track record of bispecific antibody research and development with extensive capabilities in antibody engineering and validation. We are excited by the promising clinical activity that TR009 has shown thus far, especially in heavily pre-treated patients with gastric and colon cancers, which is a key differentiator of this program. Based on our pre-clinical validation and additional biomarker work, our short-term strategy for TR009 is to pursue an accelerated approval pathway in Asia and we intend to approach both Chinese (NMPA) and Japanese regulators upon completion of our Phase 1a study in mid-2019. We also plan to simultaneously seek regulatory guidance from the FDA and EMEA for the registration of TR009 in solid tumor patients in the US and Europe."

"We are very pleased to enter into this agreement with our partners at TRIGR, a premier team that is highly experienced in taking anti-cancer drugs through clinical development and commercialization," said Sang Hoon Lee, CEO of ABL. "The dual VEGF/DLL4 bispecific antibodies currently in clinical development have all shown meaningful clinical activity even in patients who have failed or progressed on multiple lines of prior chemotherapy and VEGF-directed therapies such as Avastin and Cyramza. Across all trials, over 140 patients have been treated in monotherapy or in combination settings and we are seeing clinical benefit rates of between 50-85%. This is clearly exciting news for cancer patients worldwide."

Anti-angiogenic therapy is a cornerstone in cancer care, with sales of Avastin (an anti-VEGF antibody, Roche) and Cymraza (an anti-VEGF-R2 antibody, Eli Lilly) comprising approximately $7.5 billion in 2017. Although this class of drugs has proven survival benefits, resistance is creating the need for alternative regimens. Dual blockade of both VEFG and DLL4 is emerging as the next frontier of angiogenic therapy as the combination of these 2 mechanisms has been shown to overcome VEGF inhibitor resistance. There are 3 programs currently in clinical development targeting anti-VEGF/DLL4: AbbVie’s ABT-165 (Nasdaq: ABBV) which has recently entered Phase 2 in colorectal cancer, Oncomed’s OMP305B83 (Nasdaq: OMED) in Phase 1b in platinum-resistant ovarian cancer, and TRIGR’s TR009 in Phase 1a.

On December 3, 2018 Amgen (NASDAQ:AMGN) reported that it will present at the Citi Global Healthcare Conference at 12:35 p.m. ET on Thursday, Dec. 6, 2018, in New York City (Press release, Amgen, DEC 3, 2018, View Source;p=RssLanding&cat=news&id=2379134 [SID1234531860]). Elliott M. Levy, M.D., senior vice president of Global Development at Amgen, will present at the conference. Live audio of the presentation can be accessed from the Events Calendar on Amgen’s website, www.amgen.com, under Investors. A replay of the webcast will also be available on Amgen’s website for at least 90 days following the event

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On December 3, 2018 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic diseases, and cancer, reported initial data from its ongoing Phase 1 dose-escalation study of XmAb14045, a CD123 x CD3 bispecific antibody, in patients with relapsed/refractory acute myeloid leukemia (AML) (Press release, Xencor, DEC 3, 2018, View Source [SID1234531893]). The data were presented in an oral session at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Farhad Ravandi, M.D., Professor of Medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – MD Anderson Cancer Center.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Key Highlights

66 patients with relapsed/refractory AML received XmAb14045. Patients were a median of 61 years old and were heavily pretreated, having had a median of three prior therapies and 30% (n=20) with a history of allogeneic stem cell transplantation. 86% of patients (n=57) were refractory to their last therapy, and 53% (n=35) were categorized as adverse risk at diagnosis by the European LeukemiaNet (ELN 2017) system.
A maximum tolerated dose (MTD) has not been reached. Cytokine release syndrome (CRS) was the most common toxicity occurring in 55% of patients (n=36). 6% of patients (n=4) experienced Grade 3 or 4 CRS. CRS was more severe on the initial dose and was generally manageable with premedication. Additional adverse events consistent with CRS but not reported as such, including chills, fever, tachycardia, hypotension and hypertension within 24 hours of infusion, were reported in an additional 29% of patients (n=19).
28% of evaluable patients with AML achieved either complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the two highest initial dose levels studied (1.3 and 2.3 mcg/kg weekly; n=5/18).
Two patients with responses were bridged to stem cell transplantation, and a third transplant-ineligible patient has remained in remission for 16+ weeks after discontinuation of therapy.
"We have observed multiple complete remissions in heavily pretreated, relapsed/refractory AML patients from XmAb14045 dosed weekly, and we continue to optimize dosing regimen," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Xencor’s XmAb technology enables bispecific antibodies to retain natural antibody properties, simplifying their use and production. Our platform enables the rapid development of new bispecific antibody drug candidates addressing a breadth of targets, and throughout 2019 we anticipate several new clinical trial initiations and additional data readouts."

The data presentation is available under Archived Scientific Presentations on the Events & Presentations page in the Investors section of www.xencor.com.

Analyst & Investor Event and Webcast Information
Xencor will host an analyst and investor event tonight from 8:00 to 10:00 p.m. PST with formal remarks at 8:30 p.m. PST. The formal remarks will feature a discussion of the data presented at ASH (Free ASH Whitepaper) and Xencor’s bispecific oncology pipeline. It will be webcast live and can be accessed under Events & Presentations in the Investors section of www.xencor.com, where it will be archived for 30 days.

About XmAb14045
XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

On December 3, 2018 GlycoMimetics, Inc. (NASDAQ:GLYC) reported that new data on uproleselan-treated high risk patients with both relapsed/refractory and newly diagnosed AML were presented at an oral session during the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, GlycoMimetics, DEC 3, 2018, View Source [SID1234531812]). An analysis of clinical outcomes from the Phase 1/2 clinical study showed that uproleselan (GMI-1271) resulted in the majority of evaluable patients achieving a stringent level of measurable residual disease (MRD) negativity, an effect which translated into extended overall survival relative to matched, historical controls.1-4

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Additionally, an analysis of E-selectin ligand expression on leukemic cells demonstrated that detectable levels are present in every patient tested, providing strong clinical evidence of biological relevance in this disease setting. In bone marrow blasts, leukemic stem cell expression of E-selectin ligand correlated with leukemic blast E-selectin ligand expression (p<0.0001), consistent with the hypothesis that E-selectin-mediated interactions are a mechanism of chemoresistance. Additionally, investigators assessed the association between baseline E-selectin ligand expression and clinical outcomes using a log-rank test. In the R/R cohort of patients (n=22), this analysis demonstrated that ≥10% E-selectin ligand expression at baseline is correlated with prolonged survival (p<0.01) for patients treated with uproleselan. This observation is important since separately Chien et al. (Abstract 1513) report that high levels of E-selectin ligand in patients not treated with uproleselan correlate with worse clinical prognosis.

"The new MRD and correlative efficacy data in difficult-to-treat patients, when combined with the already encouraging response rate and survival results from this trial, further demonstrate the potential of uproleselan to be an important new treatment option in AML," said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, and the trial’s lead investigator. "The fact that more than half of the evaluable patients achieved a stringent level of MRD negativity is particularly noteworthy as uproleselan’s mechanism of action is to selectively disrupt the relationship between leukemic cells and the bone marrow microenvironment."

"It is now clearly established that patients with AML who express E-selectin ligands on their leukemic cells have more infiltrative, aggressive disease and significantly worse clinical outcomes when not treated with uproleselan," said Helen Thackray, M.D., FAAP, GlycoMimetics Senior Vice President, Clinical Development and Chief Medical Officer. "While we would expect patients with R/R AML and >10% E-selectin ligand expression on their leukemic blasts to do very poorly, it is extremely exciting to see that the addition of uproleselan is resulting in statistically significant improvements in clinical outcomes in these high-risk patients. This is completely counterintuitive to what you would expect and provides robust scientific evidence suggesting that uproleselan is exerting biologic activity."

The ASH (Free ASH Whitepaper) presentations referenced above include:

Publication Number: 331
TITLE: Uproleselan (GMI-1271), an E-Selectin Antagonist, Improves the Efficacy and Safety of Chemotherapy in Relapsed/Refractory (R/R) and Newly Diagnosed Older Patients with Acute Myeloid Leukemia: Final, Correlative and Subgroup Analyses

Publication Number: 1513
TITLE: E-Selectin Ligand Expression by Leukemic Blasts Is Associated with Prognosis in Patients with AML

References
1 Feldman et al, J Clin Oncol. 2005 Jun 20;23(18):4110-6.
2 Greenberg et al, J Clin Oncol. 2004 Mar 15;22(6):1078-86.
3 Lowenberg et al, N Engl J Med. 2009 Sep 24;361(13).
4 Lancet et al, Blood. 2014 May 22;123(21):3239-46.

About Uproleselan (GMI-1271)

Uproleselan (yoo’ pro le’sel an) is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. In a Phase 1/2 clinical trial, uproleselan was evaluated in both newly diagnosed elderly and relapsed/refractory patients with AML. In both populations, patients treated with uproleselan together with standard chemotherapy achieved better than expected remission rates and overall survival compared to historical controls, which have been derived from results from third party clinical trials evaluating standard chemotherapy, as well as lower than expected induction-related mortality rates. Treatment in these patient populations was generally well tolerated, with fewer than expected adverse effects. The U.S. Food and Drug Administration (FDA) has granted uproleselan Breakthrough Therapy Designation for the treatment of adult AML patients with relapsed/refractory (R/R) disease. GlycoMimetics is currently implementing a comprehensive development program across the clinical spectrum of AML. This includes a company sponsored Phase 3 trial in R/R AML and two consortia-sponsored trials in newly diagnosed patients. One consortium trial is being sponsored by the NCI and will enroll newly diagnosed patients fit for intensive chemotherapy. The other trial is sponsored by the HOVON group in Europe and will enroll newly diagnosed patients unfit for intensive chemotherapy.

On December 3, 2018 Sesen Bio, Inc. (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of people with cancer, reported the appointment of Dennis Kim, M.D., MPH, as chief medical officer (Press release, Sesen Bio, DEC 3, 2018, View Source [SID1234531828]). In this role, Dr. Kim will oversee the continued Phase 3 development of Vicinium, Sesen Bio’s lead targeted fusion protein, for patients with high-grade non-muscle invasive bladder cancer (NMIBC), as well as preparations for a marketing authorization submission and pre-commercial activities.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are thrilled to welcome Dennis to the Sesen Bio team and look forward to leveraging his deep drug development experience, particularly as we approach both six and 12-month data readouts from our VISTA Trial of Vicinium," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "Dennis has an extensive track record of leading product candidates through development to approval and commercial launch. As the Vicinium program advances, his leadership will be instrumental in helping us bring this novel treatment to patients in need and achieving our mission of saving and renewing the lives of people with cancer."

Dr. Kim brings significant drug development and commercialization experience to Sesen Bio’s leadership team. He has played key roles in both the approval and commercial launch of more than 10 products in oncology and immunology. Prior to joining Sesen Bio, Dr. Kim held senior and leadership roles at Ipsen, Spectrum, Novartis, Biogen Idec, and Amgen. Previously, Dr. Kim was an Epidemic Intelligence Service Officer at the Centers for Disease Control and Prevention where he played active roles in environmental and infectious disease studies. Dr. Kim earned his bachelor’s degree in chemistry and biology from Harvard, his M.D. from Stanford University and his MPH from the University of California, Los Angeles.

"I am highly encouraged by the data generated to date with Vicinium in high-grade non-muscle invasive bladder cancer, and believe this therapy has the potential to change the way we treat bladder cancer," said Dr. Kim. "I am excited to work with the Sesen Bio team and board of directors to help propel Vicinium towards a potential approval so that we can help the many patients, and their families and physicians, who need a new and effective treatment option for this devastating cancer."

In connection with the appointment of Dr. Kim, Sesen Bio entered into an employment agreement with Dr. Kim that, among other things, provides for the grant of a non-statutory stock option outside of Sesen Bio’s 2014 Stock Incentive Plan as an inducement material to Dr. Kim’s entering into employment with Sesen Bio in accordance with Nasdaq Stock Market Listing Rule 5635(c)(4). The stock option to purchase 425,000 shares of the company’s common stock is being granted effective as of December 3, 2018. The stock option grant was approved by the independent compensation committee of the board of directors in accordance with Nasdaq Stock Market Listing Rule 5635(c)(4). This stock option will have an exercise price per share equal to the closing price per share of Sesen Bio’s common stock on The Nasdaq Global Market on December 3, 2018. The stock option will have a ten-year term and will vest over a four-year period, with 25 percent of the shares underlying the stock option award vesting on the first anniversary of the date of grant and an additional 6.25 percent of the shares underlying the stock option vesting at the end of each successive three-month period following the one-year anniversary of the date of grant of the stock options, subject to Dr. Kim’s continued service with the company through the applicable vesting dates.