On April 10, 2018 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported its TTI-621 and TTI-622 clinical programs (Press release, Trillium Therapeutics, APR 10, 2018, View Source [SID1234525242]). TTI-621 and TTI-622 target CD47, a protein commonly found on the surface of cancer cells. CD47 emits a "do not eat" signal to the immune system, allowing cancer cells to evade detection.

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TTI-621 Program

TTI-621 (SIRPa-IgG1 Fc) is a decoy receptor that blocks CD47 and delivers an activating signal to effector cells such as macrophages through its IgG1 Fc region. It is being evaluated in two multi-center clinical trials using intravenous or intratumoral administration and preliminary data from both studies were reported at last year’s American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Notably, weekly infusions of TTI-621 were shown to be well tolerated and intratumoral injection was observed to reduce local lesions in 9 out of 10 patients with mycosis fungoides, a common type of cutaneous T-cell lymphoma (CTCL). Building upon these monotherapy results, Trillium has refined and focused its TTI-621 clinical program.

"Our thorough signal-seeking efforts in the TTI-621 program have successfully identified T-cell lymphoma as an indication of interest," said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. "Consequently, we are now moving forward with a more focused TTI-621 program that reflects our commitment to vigorously pursue this signal in both the intravenous and intratumoral trials."

Recent key modifications to the intravenous dosing study (TTI-621-01, NCT02663518) include:

Focusing near-term efforts on patients with CTCL and peripheral T-cell lymphoma (PTCL). These patients are being enrolled in separate cohorts that will be evaluated using a Simon 2-stage design, with a maximum of 35 subjects in each cohort.
Introducing a standardized intra-subject dose intensification schedule for all newly enrolled subjects to increase drug exposure.
Instituting a number of phase 2-like design elements, such as an independent data monitoring committee and central review of diagnostic pathology as well as radiographic disease imaging.
Recent key changes to the intratumoral dosing study (TTI-621-02, NCT02890368) include:

Increasing the duration of treatment to allow for weekly continuation therapy.
Ability to increase the size of each cohort from 12 to 40 patients based on early signs of clinical benefit.
Establishing new cohorts to study intratumoral TTI-621 in combination with a PD-1 or PD-L1 inhibitor, pegylated interferon-alpha 2a, talimogene laherparepvec (T-vec) or radiation therapy.
TTI-622 Program

TTI-622 (SIRPa-IgG4 Fc) is the second SIRPaFc decoy receptor that Trillium is advancing into the clinic. TTI-622 consists of the same CD47-binding domain of human SIRPa as TTI-621 but linked to an IgG4 Fc region, which has a more restricted ability to engage activating Fc receptors. It is expected to have a different pharmacologic profile than TTI-621 and is being developed primarily for combination therapy. Like TTI-621, TTI-622 has the advantage of minimal binding to human red blood cells, thereby reducing the risk of anemia and a large antigen sink effect.

"TTI-622 allows us to deepen our presence in the CD47 space," added Dr. Stiernholm. "With this agent we now have two SIRPaFc decoy receptors being evaluated in clinical trials, each with a different level of Fc receptor engagement. We are excited to compare and contrast the activity of these molecules and determine if each has unique applications that could benefit cancer patients."

A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma is being initiated, with the first patient expected to be dosed in Q2 2018. In the phase 1a dose-escalation part, patients will be enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b part, patients will be treated with TTI-622 in combination with rituximab, a PD-1 inhibitor or a proteasome inhibitor-containing regimen

On April 10, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that the first patient was dosed in a global Phase 2 clinical trial of tislelizumab, an investigational anti-PD-1 antibody, in patients with previously treated advanced hepatocellular carcinoma (HCC or liver cancer) (Press release, BeiGene, APR 10, 2018, View Source;p=RssLanding&cat=news&id=2341754 [SID1234525244]).

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"We have made great progress in the development of tislelizumab with three global Phase 3 trials now enrolling patients. Along with our partner, Celgene, we are encouraged by this progress and excited for the development opportunity of tislelizumab globally," commented John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene.

"This potentially registration-enabling trial of tislelizumab is expected to help us further understand its safety and efficacy with respect to the line of treatment in which it is administered to patients with advanced liver cancer. For these patients, as well as for patients in the concurrent front-line Phase 3 study of tislelizumab as compared to sorafenib, we are hopeful that tislelizumab will provide a new treatment option for a patient population with significant unmet needs," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology of BeiGene.

The Phase 2, multi-center trial is designed to evaluate the efficacy and safety of tislelizumab in patients who were previously treated for unresectable HCC. Approximately 225 patients will be enrolled at approximately 75 cancer centers internationally including Greater China (including Taiwan), the United States, and Europe. Patients will receive a 200 mg dose every three weeks.

The trial’s primary endpoint is overall response rate (ORR) evaluated by an Independent Review Committee (IRC), and secondary endpoints include duration of response (DOR), progression-free survival (PFS), disease control rate (DCR) and clinical benefit rate (CBR) assessed by IRC, and overall survival. Additional secondary endpoints include investigator assessed ORR, DOR, PFS, DCR and CBR, safety and tolerability and health-related quality of life.

"I look forward to evaluating tislelizumab for patients with advanced liver cancer, for whom the expected median survival is typically less than one year. Patients who have either not seen benefit from their front-line or even second-line treatments, or who may have lost an initial response, could potentially respond to tislelizumab. We are excited to build upon the knowledge base we have from the dose expansion cohort of patients with HCC from its Phase 1 trial," said Professor Ann-Lii Cheng, M.D., Ph.D., Distinguished Professor and Superintendent of the Cancer Center of National Taiwan University and principal investigator of the trial.

For more information about the trial, patients and physicians should email BeiGene at [email protected].

About Hepatocellular Carcinoma

HCC is a major global health problem, accounting for 85-90 percent of all reported cases of liver cancer.i Liver cancer is the sixth most common type of cancer, with an estimated 782,000 new cases per year worldwide; it was also the second most common cause of cancer-related mortality, responsible for an estimated 746,000 deaths.ii China accounts for approximately 50 percent of both new HCC cases and HCC-related deaths worldwide.ii

About Tislelizumab

Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).

On April 10, 2018 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205), a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported that it will cooperate with The University of Texas MD Anderson Cancer Center, Houston TX, to work on NBTXR3, Nanobiotix’s lead product (Press release, Nanobiotix, APR 10, 2018, www.nanobiotix.com/download/news_en/2018/MD_ANDERSON_CANCER_CENTER_AND_NANOBIOTIX_HAVE_AN_AGREEMENT_TO_RUN_IMMUNOTHERAPEUTIC_PRE-CLINICAL_RESEARCH_COMBINING_NBTXR3_AND_NIVOLUMAB.pdf#new_tab [SID1234525370]). NBTXR3 is a first-in-class product designed to destroy, when activated by radiotherapy, tumors and metastasis through physical cell death and to induce immunogenic cell death leading to specific activation of the immune system.

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This project with MD Anderson, one of the world’s leading oncological research centers, will provide an unparalleled ability to develop pre-clinical data using NBTXR3 activated by radiotherapy plus anti-PD1 Nivolumab (murine version of Opdivo).

Dr. Elsa Borghi, CMO, said: "The main objective of this collaboration is to analyze the micro environment of the tumors treated with NBTXR3 activated by radiotherapy, in order to increase and optimize the immune response."

Dr. James Welsh, MD, Associate Professor, Department of Radiation Oncology, will be the Principal Investigator and lead the research program. The project between MD Anderson and Nanobiotix will take place over the course of two years and will evaluate the use of NBTXR3 activated by radiotherapy plus anti-PD1 Nivolumab (murine version of Opdivo), provided by Bristol-Myers Squibb (BMS) in lung cancer models (in vitro and in vivo). Lung cancer is one of the most common cancer worldwide, accounting for 1.69 million deaths annually (WHO 2015).

The joint program will focus on 3 aims, leading to the maximization of NBTXR3 potential benefits in triggering an immune response:

– Evaluate the abscopal response through the combination of NBTXR3 plus an anti-PD1 antibody and radiation therapy in specific and resistent murine lung cancer models, in order to measure NBTXR3’s potential to control metastatic disease. – Evaluate if NBTXR3 can further improve T cell activation for standard radiotherapy fractions compared to SBRT, notably by determining the STING activation in vitro in cancer cells with and without NBTXR3. – Continue the characterization of the different mechanisms and types of cell death induced by NBTXR3 activated by radiation.

The joint program will also further explore the potential future use of NBTXR3 in immuno-oncology with checkpoint inhibitors, as well as its potential to control metastatic disease.
As announced in December 26, 2017, the Company has received from the Food and Drug Administration the approval of its Investigational New Drug (IND) application and should launch its first clinical trial combining NBTXR3 with immune checkpoint inhibitors in the U.S. in Q2 2018. This will be a multi-arm trial targeting a sub-population of advanced lung cancer patients and head and neck cancer patients.

NBTXR3 positioning in IO Many IO combination strategies focus on ‘priming’ the tumor, which is now becoming a prerequisite of turning a "cold" tumor into a "hot" tumor.

Compared to other modalities that could be used for priming the tumor, NBTXR3 could have a number of advantages: the physical and universal mode of action that could be used widely across oncology, a one-time local injection and good fit within existing medical practice already used as a basis for cancer treatment, as well as a very good chronic

safety profile and well-established manufacturing process.

Published preclinical and clinical data indicate that NBTXR3 could play a key role in oncology and could become a backbone in immuno-oncology.
Nanobiotix’s immuno-oncology combination program opens the door to new developments, potential new indications, and important value creation opportunities.

***

About NBTXR3

NBTXR3 is a first-in-class product designed to destroy, when activated by radiotherapy, tumors and metastasis through physical cell death and to immunogenic cell death leading to specific activation of the immune system.

NBTXR3 has a high degree of biocompatibility, requires one single administration before the whole radiotherapy treatment and has the ability to fit into current worldwide standards of radiation care.

NBTXR3 is being evaluated in head and neck cancer (locally advanced squamous cell carcinoma of the oral cavity or oropharynx), and the trial targets frail and elderly patients who have advanced cancer with very limited therapeutic options. The Phase I/II trial has already delivered very promising results regarding the local control of the tumors and a potential metastatic control through in situ vaccination.

Nanobiotix is running an Immuno-Oncology program with NBTXR3 that includes several studies. In the U.S., the Company received the FDA’s approval to launch a clinical study of NBTXR3 activated by radiotherapy in combination with anti-PD1 antibodies in lung, and head and neck cancer patients (head and neck squamous cell carcinoma and non-small cell lung cancer). This trial aims to expand the potential of NBTXR3, including using it to treat recurrent or metastatic disease.

The first market authorization process (CE Marking) is ongoing in Europe in the soft tissue sarcoma indication.

The other ongoing studies are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and prostate adenocarcinoma.

On April 10, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported that it will webcast its Quarterly Update Conference Call for the first quarter 2018 on Thurs., May 10 at 4:30 p.m. ET/1:30 p.m. PT. Dr. Helen Torley, president and chief executive officer, will lead the call (Press release, Halozyme, APR 10, 2018, View Source [SID1234525245]). On the same date, Halozyme will release financial results for the first quarter ended March 31, 2018 following the close of trading.

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The call will be webcast live through the "Investors" section of Halozyme’s corporate website and a recording will be made available following the close of the call. To access the webcast and additional documents related to the call, please visit the Investors page of www.halozyme.com approximately fifteen minutes prior to the call to register, download and install any necessary audio software. The live call may be accessed by dialing (877) 410-5657 (domestic callers) or (334) 323-7224 (international callers) using passcode 769890. A telephone replay will be available after the call by dialing (877) 919-4059 (domestic callers) or (334) 323-0140 (international callers) using replay ID number 68917761.

On April 10, 2018 Loxo Oncology (Nasdaq:LOXO) and Illumina, Inc. (Nasdaq:ILMN) reported a global strategic partnership to develop and commercialize a multi-gene panel for broad tumor profiling, resulting in a distributable, next-generation sequencing (NGS) based companion diagnostic (CDx) with a pan-cancer indication (Press release, Loxo Oncology, APR 10, 2018, View Source [SID1234525372]). The co-development partnership will seek approval for a version of the Illumina TruSight Tumor 170 as a companion diagnostic (CDx) for Loxo Oncology’s larotrectinib, which targets NTRK gene fusions, and LOXO-292, which targets RET gene alterations, across tumor types.

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TruSight Tumor 170 is a comprehensive, state-of-the-art, next-generation sequencing test that interrogates point mutations, fusions, amplifications and splice variants in 170 genes associated with common solid tumors. The CDx version of TruSight Tumor 170 will allow local laboratories to provide referring physicians with comprehensive genomic information, so that patients can be matched to the most appropriate therapeutic options. This version of TruSight Tumor 170 will run on the NextSeq 550Dx platform.

"We are leveraging our leadership in next-generation sequencing to deliver in-vitro diagnostic solutions to improve the management of cancer patients in the clinic," said Garret Hampton, Ph.D., executive vice president of clinical genomics at Illumina. "To this end, we are partnering with leading biotechnology companies, such as Loxo Oncology, to develop companion diagnostics for best-in-class therapeutics. Distributable diagnostic solutions, such as a CDx version of TruSight Tumor 170, in combination with the NextSeq 550Dx platform, will enable labs to perform precision medicine testing in-house."

Under the partnership, the companies will collaborate to validate a CDx version of TruSight Tumor 170 for NTRK fusions and RET fusions/mutations as a Class III FDA-approved diagnostic in conjunction with larotrectinib and LOXO-292, respectively. The companies are also planning to broaden the clinical utility of the full panel by obtaining regulatory approval for the other assay content, to be marketed as a tumor profiling test. Illumina will lead regulatory activities related to the Class III plans for NTRK and RET, the Class II plans for the tumor profiling content, and CE marking.

"We are very excited to announce this collaboration with Illumina, the world’s leader in NGS technology," said Jacob Van Naarden, chief business officer of Loxo Oncology. "We have piloted numerous NGS assays, and the Illumina TruSight Tumor 170 assay has consistently demonstrated robust performance with its assessment of both DNA and RNA, including highly sensitive gene fusion detection. The broad 170-gene assay content has the potential to deliver meaningful insights from a single tumor specimen, identifying patients with NTRK fusions, RET fusions, RET mutations, and many other actionable tumor alterations. Furthermore, we believe that this collaboration will improve patient access to high-quality NGS testing because pathologists will be able to run TruSight Tumor 170 locally and receive reimbursement."

About TruSight Tumor 170
TruSight Tumor 170 currently serves as the foundation for a comprehensive research use oncology menu, including:
170 unique genes informed by partnering pharmaceutical companies, academic community leaders, and industry guidance enable broad tumor profiling
Integrated workflow allowing more comprehensive testing while preserving precious samples by evaluating DNA and RNA in one integrated protocol with only 40ng from FFPE samples
Underlying assay method to serve as a standard for oncology testing and will be deployed across a variety of applications including Immuno-Oncology and liquid biopsy

About Larotrectinib (LOXO-101)
Larotrectinib is a potent, oral and highly selective tropomyosin receptor kinase (TRK) inhibitor. The investigational new drug is in clinical development for the treatment of patients with cancers that harbor a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In clinical trials, larotrectinib demonstrated marked and durable anti-tumor activity in TRK fusion cancer regardless of patient age or tumor type. In an analysis of 55 RECIST-evaluable adult and pediatric patients with NTRK gene fusions, larotrectinib demonstrated an 80 percent investigator-assessed confirmed overall response rate (ORR) and a 75 percent centrally-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib was well tolerated; the majority of all adverse events were grade 1 or 2. There were no treatment-related grade 4 or 5 events, and no treatment-related grade 3 adverse events occurred in more than 5% of patients.
Larotrectinib has been granted Breakthrough Therapy Designation, Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA.

In November 2017, Loxo Oncology and Bayer entered into an exclusive global collaboration for the development and commercialization of larotrectinib and LOXO-195, a next-generation TRK inhibitor. Bayer and Loxo Oncology will jointly develop the two products with Loxo Oncology leading the ongoing clinical studies as well as the filing in the U.S., and Bayer leading ex-U.S. regulatory activities and worldwide commercial activities. In the U.S., Loxo Oncology and Bayer will co-promote the products.

For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

About LOXO-292
LOXO-292 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary thyroid cancer, and a subset of colon and other cancers. RET point mutations account for approximately 60% of medullary thyroid cancer. Both RET fusion and select RET mutated cancers are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 is currently being studied in a Phase 1 trial. Interested patients and physicians can contact the Loxo Oncology Physician and Patient RET Clinical Trial Hotline at 1-855-RET-4-292 or email [email protected].

About Illumina
Illumina is improving human health by unlocking the power of the genome. Our focus on innovation has established us as the global leader in DNA sequencing and array-based technologies, serving customers in the research, clinical, and applied markets. Our products are used for applications in the life sciences, oncology, reproductive health, agriculture, and other emerging segments. To learn more, visit www.illumina.com and follow @illumina.