On December 4, 2017 Kymab’s reported that data at the British Society for Immunology Congress demonstrates efficient identification and validation of human antibodies (Press release, Kymab, DEC 4, 2017, View Source [SID1234537007])

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Three poster presentations at the 2017 British Society for Immunology Congress describe how Kymab’s efficient human antibody platforms were able to identify an anti-PD-L1 antibody, KY1003, and show it was an effective anti-tumour antibody in in vitro and in vivo models.

In Rachael Kimber’s poster, Cell based screening cascade to select anti-human PD-L1 antibodies, the team describe a cell-based, in vitro screening cascade that enabled functional characterisation of anti-human PD-L 1 antibodies.

They identified a panel of potent fully human, antagonistic antibodies that bind human and cynomolgus PD-L1 and enhance T-cell activity, identifying a lead clone, KY1003, that has the characteristics of a clinically relevant PD-L1 antibody.

Lucy Hepburn presents Development and characterization of a human T cell:tumour cell co-culture assay for assessment of immunomodulatory antibodies, which suggests that prolonged co-culture of human T-cells with the A375 tumour cell line, designed to mimic chronic antigen stimulation, generates T-cells that appear ‘exhausted’.

By using these T-cells, the team confirm that Kymab’s anti-PD-L1 antibody, KY1003, can enhance in vitro T-cell killing of A375 cells and inhibit immunosuppressive PD-1/PD-L1 signalling to increase tumour elimination by T cells in vivo.

Morgane Lecointre’s poster, Development of a "tumour-educated" T cell killing assay for predictive in vitro assessment of anti-PD-L1 antibodies, demonstrates how KY1003 can revert T-cell exhaustion in in vitro models using A375 tumour cells.

Importantly, KY1003 shows a strong anti-tumour efficacy in an in vivo human melanoma xenograft model. The approach is biologically relevant in validation of antibodies that target T-cell immune-modulatory molecules.

Notes to Editors
PDF versions of the posters
Cell based screening cascade to select anti-human PD-L1 antibodies (0.5 MB: Kimber et al., Poster P074)
Development and characterization of a human T cell:tumour cell co-culture assay for assessment of immunomodulatory antibodies (0.7 MB: Hepburn et al., Poster P077)
Development of a "tumour-educated" T cell killing assay for predictive in vitro assessment of anti-PD-L1 antibodies (4.3 MB: Lecointre et al., Poster P075)

On December 4, 2017 Seattle Genetics, Inc. (NASDAQ:SGEN) reported that the company will webcast an investor and analyst event on Monday, December 11, 2017 during the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, GA (Press release, Seattle Genetics, DEC 4, 2017, View Source;p=RssLanding&cat=news&id=2320818 [SID1234522352]). Industry experts will discuss the ADCETRIS (brentuximab vedotin) phase 3 ECHELON-1 data, and members of the Seattle Genetics management team will discuss other program highlights.

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The event will take place from approximately 8:30 p.m. to 9:30 p.m. Eastern Time. The webcast will be available live and for replay from Seattle Genetics’ website at www.seattlegenetics.com in the Investors section.

On December 4, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported updated clinical data from the larotrectinib pediatric Phase 1 SCOUT clinical trial (Press release, Loxo Oncology, DEC 4, 2017, View Source [SID1234522348]). These data are being presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Pediatric Cancer Research in Atlanta.

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"Targeted therapy success stories in pediatric oncology are uncommon, and larotrectinib has invigorated the pediatric oncology community," said Brian Turpin, D.O., the presenting SCOUT principal investigator and assistant professor in the division of oncology at Cincinnati Children’s Hospital. "Larotrectinib’s near universal response rate and compelling durability of response in pediatric patients with TRK fusion cancers is likely to be practice changing. Furthermore, the first-ever TRK inhibitor response in a TRK fusion glioblastoma patient highlights the potential for larotrectinib in TRK fusion central nervous system tumors."

"We are grateful to the children and families who have enabled the development of larotrectinib through their participation in clinical trials," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology.

As of a July 17, 2017 data cut-off date, 24 pediatric patients were enrolled in the dose escalation portion of the Phase 1 trial, including 17 patients with TRK fusion cancers. TRK fusion patients carried primary diagnoses of infantile fibrosarcoma, thyroid cancer, and various soft tissue sarcomas.

TRK Fusion Patients (n=17)* Patients without TRK Fusions (n=7)
Independent Review Committee Assessed Response Investigator Assessed Response Investigator Assessed Response
Overall Response Rate
(ORR = PR+CR) 93%
(95% CI: 68% – 100%) 93%
(95% CI: 68% – 100%) 0%
Partial Response (PR) 80% 67%** 0%
Complete Response (CR) 13% 27% 0%
Stable Disease 7% 7% 0%
Progressive Disease 0% 0% 100%
* 2 patients not evaluable due to having non-measurable disease at baseline.
** Includes 2 patients with unconfirmed partial responses as of July 17, 2017, which were subsequently confirmed.

Among the 17 patients with TRK fusion cancers, 94% either remain on drug or received surgery with curative intent; four patients have been followed greater than one year and 12 have been followed greater than six months.

The larotrectinib adverse event profile is consistent with data previously presented publicly. The most common treatment-related adverse events at the Phase 2 dose included increased liver function tests, neutropenia, and nausea, all largely grade 1.

These data are being presented in a poster session on December 4, 2017 and an oral presentation on December 5, 2017. The poster and presentation will be available online at View Source at the time of their scheduled presentations.

About Larotrectinib (LOXO-101)
Larotrectinib is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). 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 an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 75 percent independently-reviewed confirmed overall response rate (ORR) and an 80 percent investigator-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib has been granted Breakthrough Therapy Designation Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA. 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.

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. Loxo Oncology leads worldwide development and U.S. regulatory activities. Bayer leads ex-U.S. regulatory activities and worldwide commercial activities. In the U.S., Loxo Oncology and Bayer will co-promote the products.

About TRK Fusion Cancer
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

On December 3, 2017 Vernalis plc (LSE: VER) reported that it has entered into a drug discovery collaboration with Daiichi Sankyo Company, Limited utilizing Vernalis’ fragment and structure-based drug discovery platform against undisclosed oncology targets (Press release, Vernalis, DEC 3, 2017, http://www.vernalis-research.com/respubs/research-press-releases/729-vernalis-plc-enters-into-research-collaboration-with-daiichi-sankyo [SID1234531525]).

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The financial terms of this collaboration are not disclosed.

Ian Garland, CEO of Vernalis, commented: "We are delighted to be working with Daiichi Sankyo on this project. This is another excellent endorsement of our market leading fragment and structure-based drug discovery platform and we look forward to a successful collaboration with Daiichi Sankyo."

On December 3, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has approved FoundationOne CDx, Foundation Medicine’s comprehensive companion diagnostic assay for personalised oncology care1 (Press release, Hoffmann-La Roche, DEC 3, 2017, View Source [SID1234522343]). FoundationOne CDx supports physicians in clinical decision-making by providing a report that describes the unique genomic profile of the patient’s tumour as well as associated approved therapies and relevant clinical trial information. FDA approval of this assay, based on its clinical and analytical validation, now means the service can be used as a companion diagnostic for therapy selection when people have been diagnosed with solid tumours.

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"The approval of FoundationOne CDx represents a major advance in the personalisation of cancer care, facilitating access for patients in the US to a comprehensive pan-tumour companion diagnostic that will help identify approved treatment options based on the molecular footprint of each individual’s cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Our belief is that profiling will increasingly become routine in clinical practice, so we have worked closely with Foundation Medicine to develop an extensive clinically and analytically validated platform that can support both existing and future companion diagnostic needs."

FoundationOne CDx is the first FDA-approved pan-tumour comprehensive companion diagnostic assay to:

assess all four classes of genomic alterations in 324 genes known to drive cancer growth, providing information to help guide the decisions of treating physicians;

identify patients with advanced cancer who are likely to respond to targeted therapies, based on their individual genomic profile; and,

report genomic signatures, including microsatellite instability (MSI) and tumour mutational burden (TMB), and report genomic alterations in other genes [relevant to other therapies] for use by physicians for patient management according to professional guidelines in oncology.

Of the 17 therapies currently approved for inclusion in the report, twelve are approved as first-line treatment options for their respective indications. The number of on-label targeted therapies in the report is expected to increase over time as Foundation Medicine and its partners gain FDA approval for additional biomarkers on the platform.
The approval of FoundationOne CDx also represents the first next generation sequencing (NGS)-based companion diagnostic for Alecensa (alectinib), an FDA-approved monotherapy for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC)2. Alecensa is approved in both the front-line setting and for people who have progressed on or are intolerant to crizotinib. Including ALK-rearrangements in a larger comprehensive panel may ensure that more patients are identified and eligible for treatment based on their ALK-positive status.

Roche acquired a majority stake in Foundation Medicine in April 2015, and since then, has been actively commercialising Foundation Medicine’s portfolio of services in countries outside the US, with more than 20 countries on three continents already having launched FoundationOne.

About FoundationOne CDx
FoundationOne CDx is a comprehensive genomic profiling service for solid tumours that provides potentially actionable information with the molecular profiling of 324 genes known to drive cancer growth. FoundationOne CDx is intended to be used as a comprehensive companion diagnostic for patients with certain types of NSCLC, melanoma, colorectal cancer, ovarian cancer or breast cancer to identify those patients that may benefit from treatment with one of 17 targeted therapies following the detection of alterations in the EGFR, ALK, BRAF, ERBB2, KRAS, NRAS, and BRCA1/2 genes.

FoundationOne CDx is an NGS-based in vitro diagnostic for detection of base substitutions, insertion and deletion alterations (indels), copy number alterations (CNAs) and select gene rearrangements in 324 genes, as well as genomic signatures including MSI and TMB, using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumour tissue specimens. FoundationOne CDx is intended to be used by physicians as decision-making support in consideration of a patient’s genomic profile for therapy selection and patient management according to professional guidelines in oncology for cancer patients.