On December 4, 2018 Amgen (NASDAQ:AMGN) reported the first clinical results from studies evaluating investigational novel bispecific T cell engager (BiTE) immunotherapies AMG 420 and AMG 330 (Press release, Amgen, DEC 4, 2018, View Source;p=RssLanding&cat=news&id=2379192 [SID1234531859]). In two separate Phase 1 dose escalation studies, AMG 420, which targets B-cell maturation antigen (BCMA), and AMG 330, which targets CD33, provided early evidence of tolerability and anti-tumor activity in patients with relapsed and/or refractory multiple myeloma and relapsed or refractory acute myeloid leukemia (AML), respectively. These data were highlighted during oral presentations at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego.

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BiTE antibody construct technology, pioneered by Amgen, is an innovative treatment approach that helps the body’s immune system attack cancer cells without the removal of immune cells from the patient. Amgen is studying a number of "off-the-shelf" investigational BiTE immunotherapies, with distinct targets, across a range of hematologic and solid tumors.

"Building on our success with the only approved BiTE immunotherapy available for patients, Amgen is emphasizing our commitment to the potential of this platform by advancing the development of approximately a dozen novel molecules across hematologic and solid tumor targets in hopes of continuing to offer meaningful advances to patients in need," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We’re encouraged by the early results of investigational BiTE immunotherapies AMG 420 and AMG 330, especially when considered in the context of these heavily pre-treated patients, many of whom have run out of available options. We look forward to sharing more results from our BiTE pipeline at future medical meetings."

ASH Abstract #1010: Treatment with AMG 420, an anti-B-Cell Maturation Antigen (BCMA) Bispecific T-cell Engager (BiTE) Antibody Construct, Induces Minimal Residual Disease (MRD) Negative Complete Responses in Relapsed and/or Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a First-in-Human (FIH) Phase 1 Dose Escalation Study

The data shared at ASH (Free ASH Whitepaper) were the first presentation of all endpoints from this Phase 1 dose-escalation trial of AMG 420 in patients with relapsed and/or refractory multiple myeloma. The objectives of the study included assessment of safety, tolerability and anti-tumor activity of AMG 420 per International Myeloma Working Group 2006 Uniform Response Criteria for Multiple Myeloma.

In the study, 42 patients with relapsed and/or refractory multiple myeloma who had progression after at least two prior lines of treatment (including a proteasome inhibitor and an immunomodulatory imide drug) received AMG 420 at varying doses [0.2 to 800 µg/day (d)]. AMG 420 induced clinical responses in 13 patients, including complete responses (CR) in seven patients. Four patients treated at the 400 µg/d dose achieved minimal residual disease (MRD) negative complete responses, meaning that no cancer cells were detectable in the bone marrow. The objective response rate at 400 µg/d was 70 percent (seven of 10 patients), with six patients still responding up to 7.5 months. One dose-limiting toxicity was observed up to the 400 µg/d dose (peripheral polyneuropathy, which improved to baseline after intravenous immunoglobulin and corticosteroid treatment).

Of those patients with serious adverse events (AEs) (n=20, 48 percent), 17 required hospitalization and four had prolonged hospitalization. Serious AEs included infections (n=12), peripheral polyneuropathy (n=2), and one each of liver failure, cardiac failure, edema, biliary obstruction, spinal cord compression, renal failure and weight loss. Treatment-related serious AEs included polyneuropathy (n=2, both grade 3) and edema (n=1, grade 3). Cytokine release syndrome (CRS) was seen in 16 patients (grade 1, n=13; grade 2, n=2; grade 3, n=1). In this study, 800 µg/d was determined to not be tolerable, as two out of the three patients treated at this dose experienced dose-limiting toxicities.

Two patients died during the course of the study from AEs not considered treatment-related. One patient died after the first cycle of treatment from acute respiratory distress due to concurrent flu and aspergillosis. The second patient died from liver failure secondary to a viral infection during the course of treatment.

"These first-in-human data of a BCMA-targeting BiTE immunotherapy showed encouraging evidence of AMG 420 activity, with no major toxicities up to the 400 µg/d dose in patients with relapsed and/or refractory multiple myeloma who received a median of four prior therapies," said Max S. Topp, M.D., professor, Hospital of Wuerzburg, Germany and AMG 420 clinical study investigator. "Despite recent treatment advances, multiple myeloma continues to be a disease characterized by cycles of relapse and recurrence requiring additional therapies to help control the disease."

Additionally, AMG 420 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA). Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.

ASH Abstract #25: A Phase 1 First-in-Human Study of AMG 330, an Anti-CD33 Bispecific T-cell Engager (BiTE) Antibody Construct, in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

In a separate first-in-human Phase 1 dose escalation study, 40 patients with relapsed or refractory AML were enrolled to receive AMG 330 in 12 dose cohorts with a target dose range of 0.5 to 480 µg/d. The study objectives were to evaluate the safety, pharmacokinetics and pharmacodynamics of AMG 330 and to estimate the maximum tolerated dose. Results showed that two patients in the trial achieved a CR at the 240 µg/d dose and two patients achieved a CR with incomplete blood count recovery, one at the 240 µg/d dose and one at the 120 μg/d dose. The CRs were not sustained beyond one cycle of treatment.

Patients in the trial received a median of one (range: 1-6) cycle with AMG 330; the majority of patients discontinued treatment for disease progression. Other reasons for study discontinuation included AEs (n=6, 2 treatment-related) and patient request (n=2).

Serious AEs were seen in 73 percent of patients (treatment-related in 17 patients). The most common serious AEs seen in more than one patient included CRS (n=11), febrile neutropenia (n=7), pneumonia (n=4), leukopenia (n=4), pyrexia (n=3), thrombocytopenia (n=3) and subdural hematoma (n=2). One patient died on study due to AML progression and one due to intracranial hemorrhage (neither treatment-related). There were dose-limiting toxicities of grade 2 CRS and grade 4 ventricular fibrillation with a target dose of 480 μg/d administered as a single-step regimen.

"The majority of adult AML patients will not be cured with standard chemotherapy, underscoring the need for innovative treatment options for those who have relapsed or are refractory to currently available treatments1," said Farhad Ravandi, M.D., Janiece and Stephen A. Lasher professor of medicine and chief of section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – MD Anderson Cancer Center and AMG 330 clinical study investigator. "These early data are encouraging as they indicate AMG 330 may have anti-leukemic activity in heavily pretreated patients with relapsed or refractory AML, validating the need for continued evaluation of the BiTE platform in targeting CD33."

About BiTE Technology
Bispecific T cell engager (BiTE) antibody construct is an innovative technology that can be engineered to target any tumor antigen expressed by any type of cancer. The protein molecules are designed to kill malignant cells using the patient’s own immune system by bridging T cells to tumor cells. BiTE antibody construct helps connect the T cells to the targeted cell, with the intent of causing T cells to inject toxins which trigger cancer cell death (apoptosis). Amgen is developing BiTE antibody constructs to uniquely (or specifically) target numerous hematologic malignancies and solid tumors.

On December 4, 2018 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported new preclinical data on the Company’s induced pluripotent stem cell (iPSC) product platform and its iPSC-derived, off-the-shelf cell-based cancer immunotherapy pipeline at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Fate Therapeutics, DEC 4, 2018, View Source [SID1234531876]). Last week, the Company announced that the U.S. Food and Drug Administration (FDA) allowed its Investigational New Drug (IND) Application for FT500, the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master iPSC line. The clinical trial of FT500 is expected to be the first-ever clinical investigation in the U.S. of an iPSC-derived cell product.

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"Fate Therapeutics is at the forefront in developing off-the-shelf, cell-based cancer immunotherapies, and is rapidly progressing multiple iPSC-derived CAR T- and NK cell product candidates that have the potential to disrupt autologous and allogeneic approaches to cell therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "The clearance of our FT500 IND by the FDA is a landmark achievement and serves as a roadmap for advancement of our iPSC-derived cell product pipeline into clinical development. We believe the use of clonal master iPSC lines uniquely enables the production of multi-functional, cell-based cancer immunotherapies that are uniformly engineered, are available for off-the-shelf administration to patients and can be effectively combined in multi-dose, multi-cycle regimens with well-established immune-oncology agents, such as checkpoint inhibitor blockade and monoclonal antibody therapy, including in earlier lines of therapy."

Several of the Company’s iPSC-derived cell product candidates undergoing development were discussed during an investor event at ASH (Free ASH Whitepaper) by its collaborating experts in the field of cell-based cancer immunotherapy including:

Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering & Gene Transfer and Gene Expression Laboratory, Memorial Sloan Kettering Cancer Center;

Jeffrey S. Miller, M.D., Deputy Director, Masonic Cancer Center, University of Minnesota; and

Dan S. Kaufman, M.D., Ph.D., Professor of Medicine, Division of Regenerative Medicine, Director of Cell Therapy, University of California – San Diego.
FT500
The clinical trial of FT500 is intended to evaluate the safety and tolerability of multiple doses of FT500, in multiple dosing cycles with nivolumab, pembrolizumab or atezolizumab, in subjects that have progressed or failed on immune checkpoint blockade (CPB) therapy. Although CPB therapy can lead to prolonged responses, refractory disease and progression after initial response remain major causes of mortality. In patients receiving CPB therapy, mutations in beta-2-microglobulin (B2M), an essential component for the stable presentation of antigens by tumor cells, have been identified in approximately 30% of patients with progressing disease and are associated with poor overall survival. Investigators have demonstrated in various tumor model systems that NK cells have the potential to rescue CPB therapy by recognizing and killing B2M-deficient target cells. An oral presentation at ASH (Free ASH Whitepaper) by Dr. Miller showed that FT500 synergizes with T cells and anti-PD1 antibody to produce pro-inflammatory cytokines and completely clear target cancer cells in an in vitro three-dimensional tumor spheroid model.

FT516
FT516 is a universal, off-the-shelf NK cell product candidate manufactured from a clonal master iPSC line engineered to uniformly express a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor. Since CD16 binds the Fc region of tumor-bound antibodies, FT516 can be combined with FDA-approved monoclonal antibody therapies to target a broad spectrum of tumor-associated antigens. In preclinical studies, FT516 exhibits potent and persistent anti-tumor activity in vitro and in vivo against multiple tumor types, including in combination with monoclonal antibody therapies that target CD20, HER2 and EGFR. The Company plans to submit an IND to the FDA by the end of 2018 to evaluate the safety and tolerability of multiple doses of FT516 in multiple dosing cycles in combination with FDA-approved monoclonal antibody therapy.

FT596
FT596 is a universal, off-the-shelf chimeric antigen receptor (CAR) NK cell product candidate that expresses a proprietary CAR targeting CD19, a novel IL-15 receptor fusion for cytokine-independent persistence, and a hnCD16 Fc receptor for augmented antibody-dependent cellular-cytotoxicity (ADCC). A poster presentation at ASH (Free ASH Whitepaper) by scientists from the Company and the University of California – San Diego highlighted new in vivo data demonstrating that FT596 displays long-term persistence without systemic cytokine support. Additionally, FT596 prevents tumor progression and promotes sustained long-term survival in a B-cell leukemia xenograft model. Moreover, as proof-of-concept for the mitigation of antigen escape, FT596 in combination with rituximab completely eliminates CD19+ and CD19- B-cell tumor cells in a co-culture cytotoxicity assay.

FT538
FT538 is a universal, off-the-shelf NK cell product candidate that expresses both a novel IL-15 receptor fusion for cytokine-independent persistence and a hnCD16 Fc receptor for augmented ADCC, and additionally lacks CD38 expression to eliminate fratricide when combined with CD38-targeting monoclonal antibody therapy. A poster presentation at ASH (Free ASH Whitepaper) by scientists from the Company and the University of Minnesota highlighted new in vitro data showing that FT538 in combination with daratumumab is resistant to fratricide and eliminates multiple myeloma cancer cells in a serial re-challenge assay. The Company is investigating the additional therapeutic benefit of including a novel humanized CAR targeting B-cell Maturation Antigen (BCMA) as a dual-targeting mechanism to address multiple myeloma and other BCMA-positive malignancies.

FT819
FT819 is an off-the-shelf, TCR-less CD19 CAR T-cell product candidate manufactured from a clonal master iPSC line that is undergoing preclinical development under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Dr. Sadelain. FT819 is engineered to completely eliminate expression of the T-cell receptor and to insert a next-generation CAR receptor into the T-cell receptor alpha locus, a strategy which is intended to convey enhanced safety and efficacy while eliminating the possibility of graft-versus-host disease. A poster presentation at ASH (Free ASH Whitepaper) by scientists from the Company and MSK showcased new in vivo data demonstrating that FT819, when thawed and directly infused, effectively controls tumor progression comparable to peripheral blood CAR T cells in a preclinical mouse model of acute lymphoblastic leukemia.

A copy of the Company’s presentation from its ASH (Free ASH Whitepaper) investor event can be accessed under "Events & Presentations" in the Investors & Media section of the Company’s website at www.fatetherapeutics.com.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary iPSC product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event, and selecting a single iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf to treat many patients. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 100 issued patents and 100 pending patent applications.

On December 4, 2018 Cofactor Genomics, a clinical RNA sequencing and translational assay developer, reported a pilot study to evaluate use of Cofactor’s ImmunoPrismTM assay in Genocea Biosciences’ Phase 1/2a clinical trial testing the safety and efficacy of its lead personalized cancer vaccine candidate, GEN-009, in adult cancer patients with a variety of solid tumors (Press release, Cofactor Genomics, DEC 4, 2018, View Source [SID1234531892]).

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The pilot study is designed to enable Genocea to comprehensively characterize the immune responses that patients enrolled in the clinical trial generate in response to vaccination. The RNA-based assay developed by Cofactor should enable Genocea to compare the immune cell composition for 8 major immune types within and between patients, including expression reporting for key immune escape genes.

"We are working to develop truly effective personalized neoantigen vaccines with which to treat cancer patients. Through exploration of advanced technologies like Cofactor’s ImmunoPrism assay, we aim to better understand the intratumoral immune responses we are eliciting in response to our vaccine," said Jessica Baker Flechtner, Ph.D., Chief Scientific Officer at Genocea.

"Pilot studies such as this one, where our technology is implemented in the field to empower drug developers to find the most robust markers of therapeutic success, are extremely important in validating our cutting-edge technology," noted David Messina, Chief Operating Officer at Cofactor Genomics. "Demonstrating the utility of a new approach to immune profiling is best accomplished with partners like Genocea, who are eager to gain access to the most innovative and advanced assays."

Cofactor Genomics recently announced the release of their ImmunoPrism Immune Profiling Kit, which enables access to their proprietary molecular and machine-learning informatics for RNA analysis of the tumor microenvironment. The ImmunoPrism kit offers laboratories the ability to validate the assay, as Cofactor has done through their CAP-accredited laboratory.

Cofactor will present the results of this clinical validation work during an upcoming webinar titled, "Clinical Validation of a Multidimensional Pan-Cancer Immune Assay" on Thursday, December 13 at 11 AM EST: View Source

On December 3, 2018 Geron Corporation (Nasdaq: GERN) reported that updated results from Part 1 of IMerge, the Phase 2 portion of a Phase 2/3 clinical trial of imetelstat in lower risk myelodysplastic syndromes (MDS), were presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California on December 2, 2018 (Press release, Geron, DEC 3, 2018, View Source [SID1234531827]). The oral presentation was made by David Steensma, M.D., Institute Physician at the Dana-Farber Cancer Institute and Associate Professor at Harvard Medical School, and an IMerge clinical investigator. Geron believes these results support initiating the Phase 3 portion of IMerge to address an unmet medical need for patients for whom erythropoiesis stimulating agents (ESAs) are not effective and for whom currently available therapies show only modest efficacy.

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"The results from the Phase 2 portion of IMerge presented at ASH (Free ASH Whitepaper) highlight imetelstat’s broad clinical activity, especially in difficult-to-treat patients, as indicated by the high baseline transfusion burden of the patients enrolled in IMerge. As such, we believe imetelstat could offer a much-needed alternative treatment in lower risk MDS," said John A. Scarlett, M.D., Geron’s President and Chief Executive Officer. "We remain committed to developing imetelstat and continue to plan the initiation of the Phase 3 portion of IMerge by mid-year 2019."

IMerge Phase 2/3 Clinical Trial Design

IMerge is a two-part clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk MDS who have relapsed after or are refractory to prior treatment with an ESA. The first part of the trial was originally designed as a Phase 2, open-label, single-arm trial to assess the efficacy and safety of imetelstat. The second part of the trial is planned as a Phase 3 double-blind, randomized, placebo-controlled trial in approximately 170 patients. To be considered for enrollment into IMerge, patients had to be transfusion dependent, requiring ≥4 units of red blood cells (RBC) over 8 weeks prior to entry into the trial. The primary efficacy endpoint of the trial is the rate of RBC transfusion-independence (RBC TI) lasting at least 8 weeks, defined as the proportion of patients without any RBC transfusion during any consecutive 8 weeks since entry into the trial. Key secondary endpoints are the rate of ≥24-week RBC TI and the rate of hematologic improvement-erythroid (HI-E), defined as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least 8 weeks or a reduction of at least 4 units of RBC transfusions over 8 weeks compared with the prior RBC transfusion burden.

Among the first 32 patients enrolled in the Phase 2 portion of IMerge, an initial cohort of 13 patients, who were non-del(5q) and naïve to HMA and lenalidomide treatment, showed an increased RBC TI rate and durability compared to the overall trial population. Thus, earlier this year, an additional expansion cohort of 25 patients were enrolled who were non-del(5q) and naïve to HMA and lenalidomide treatment in order to increase the experience and confirm the benefit-risk profile of this target patient population.

Clinical Data Presentation

Title: Imetelstat Treatment Leads to Durable Transfusion Independence (TI) in RBC Transfusion-Dependent (TD), Non-Del(5q) Lower Risk MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Who Are Lenalidomide and HMA Naïve (Abstract #463)

The oral presentation described combined data with a data cut-off date of October 26, 2018 for the target patient population (n=38) in the Phase 2 portion of IMerge, which includes 13 patients from the initial cohort and 25 patients from the expansion cohort. The initial cohort had a median follow up time of 29 months, and the expansion cohort had a median follow up of almost nine months. As of the data cut-off date, median duration of RBC TI had not been reached for the target patient population. Geron expects further data from the Phase 2 portion of IMerge for the target patient population reflecting longer follow up to be available in 2019 and anticipates submitting such data for presentation at a future medical conference.

Efficacy Highlights for Target Patient Population (n=38):

37% (14/38) of patients achieved ≥8-week RBC TI
26% (10/38) of patients achieved ≥24-week RBC TI
Rate of transfusion reduction (HI-E) was 71% (27/38)
Mean relative reduction of RBC transfusion burden from baseline was 68%
Broad clinical activity observed
• Similar 8-week RBC TI was observed in patients with baseline serum erythropoietin (sEPO) levels less than or greater than 500mU/mL
• 8-week RBC TI consistent across ring-sideroblast (RS) patient subtypes, RS+ and RS-
Reductions in mutation burden and presence of RS noted among responding patients, suggesting potential disease modifying activity
Safety Summary for Target Patient Population (n=38):

Cytopenias, particularly neutropenia and thrombocytopenia, were the most frequently reported adverse events which were predictable, manageable and reversible
The slides from the oral presentation at ASH (Free ASH Whitepaper) are available on Geron’s website at www.geron.com/r-d/publications.

Phase 3 Development Plan for Lower Risk MDS

Based on the combined data from the initial and expansion cohorts for the target patient population in the Phase 2 portion of IMerge, Geron plans to initiate the Phase 3 portion of IMerge after the sponsorship of the ongoing imetelstat clinical trials has been transferred back to Geron. Geron anticipates patient screening and enrollment for the Phase 3 portion of IMerge to begin by mid-year of 2019.

Analyst and Investor Event

On December 10, 2018, Geron will host a webcasted event for analysts and investors. At the event, Dr. Azra Raza, a clinical investigator for IMerge, will reprise the oral presentation made at the ASH (Free ASH Whitepaper) Annual Meeting, as well as describe the unmet medical need in lower risk MDS. A live audio webcast of the event will be available on Geron’s website, www.geron.com/investors/events. If you are unable to listen to the live presentation, an archived webcast of the event will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat include a Phase 2/3 trial called IMerge in lower risk myelodysplastic syndromes (MDS) and a Phase 2 trial called IMbark in Intermediate-2 to High-risk myelofibrosis. Imetelstat received Fast Track designation from the United States Food and Drug Administration for the treatment of patients with transfusion-dependent anemia due to lower risk MDS who are non-del(5q) and refractory or resistant to an erythroid stimulating agent

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.

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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.