On December 19, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Commission has approved Kadcyla (trastuzumab emtansine) for the adjuvant (after surgery) treatment of adult patients with HER2-positive early breast cancer (eBC) who have residual invasive disease in the breast and/or lymph nodes after neoadjuvant (before surgery) taxane-based and HER2-targeted therapy (Press release, Hoffmann-La Roche, DEC 19, 2019, View Source [SID1234552491]).

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"Optimal treatment is vital for every patient with early-stage breast cancer, a setting where cures are possible," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "This approval of Kadcyla will allow many more women with HER2-positive early breast cancer to be given a transformative treatment that may cut the risk of their disease returning or progressing."

The goal of neoadjuvant treatment is to shrink tumours in order to help improve surgical outcomes. Adjuvant treatment aims to eliminate any remaining cancer cells in the body to help reduce the risk of the cancer returning.1 People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease.2

The approval of Kadcyla in Europe is based on results from the phase III KATHERINE study, which showed that Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.001) compared to Herceptin (trastuzumab) as an adjuvant treatment in people with HER2-positive eBC who have residual invasive disease after neoadjuvant taxane and Herceptin-based treatment. At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an absolute improvement of 11.3%. The safety profile of Kadcyla was consistent with that observed in previous studies.3

The impact of adjuvant treatment with Kadcyla has already been seen in the US where thousands of women are already being given this treatment following US Food and Drug Administration approval in May.4 Kadcyla in this setting is now approved in 27 countries worldwide and the use of Kadcyla in eBC has been recommended by multiple treatment guidelines, including those from the St Gallen International Breast Cancer Conference, the AGO and the NCCN.5,6,7

About the KATHERINE study8
KATHERINE is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive eBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which in this study is defined as the time from randomisation to the time that the patient is free from invasive breast cancer recurrence, or death from any cause. Secondary endpoints include iDFS including second primary non-breast cancer, disease-free survival and overall survival.

About Kadcyla
Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells, potentially limiting damage to healthy tissues. It combines two anti-cancer properties joined together by a stable linker: the HER2-targeting properties of trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1.9 Kadcyla is the only ADC approved as a single agent in over 100 countries, including the US and EU, for the treatment of people with HER2-positive metastatic breast cancer who have previously received Herceptin and taxane-based chemotherapy, separately or in combination. Kadcyla is also approved in the US for the adjuvant treatment of people with HER2-positive eBC with residual invasive disease after neoadjuvant treatment that included Herceptin and taxane-based chemotherapy. Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and advanced HER2-positive breast cancer. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.10 Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test which identifies people who will likely benefit from these medicines at the onset of their disease.

On December 18, 2019 Nordic Nanovector ASA (OSE: NANO) reported that its research and development project Nanoyield has received a non-dilutive funding of NOK 12 million (USD 1.3 million) from the Norwegian Research Council (Forskningsrådet) (Press release, Nordic Nanovector, DEC 18, 2019, View Source [SID1234553441]).

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The Nanoyield project is aimed at optimising the production yield of Nordic Nanovector’s CD37-targeting antibody NNV003. The NNV003 antibody is the antibody component of the radioimmunoconjugate Alpha37. The project will be conducted in partnership with SINTEF Biotechnology (Trondheim, Norway), one of Europe’s largest independent research institutes.

Nordic Nanovector recently received grant funding of EUR 0.6 million from Eurostars, a Europe-wide R&D funding programme, to advance the Alpha37 programme.

Alpha37 comprises NNV003 with the alpha-particle generator lead-212 (212Pb) and is being developed in an R&D collaboration with Orano Med. Preclinical data presented at international cancer congresses during the past 12 months have shown that a single injection of Alpha37 is well-tolerated and produces a promising anti-cancer effect and subsequent improvement on survival in preclinical models of CD37-positive chronic lymphocytic leukaemia (CLL) and non-Hodgkin’s lymphoma (NHL).

Jostein Dahle, Chief Scientific Officer of Nordic Nanovector, said: "We are excited to receive this new non-dilutive grant funding from Forskningsrådet to advance the Alpha37 programme. Alpha-emitting radionuclides have demonstrated good potential for targeted cancer therapies because their high energy is limited to a few cell widths resulting in localised cytotoxicity while sparing surrounding healthy tissues. We have seen very encouraging preclinical evidence demonstrating the potential of Alpha37 to treat CLL and NHL and with our partners are advancing this exciting candidate towards clinical trials in these indications."

On December 18, 2019 Pathios Therapeutics Limited ("Pathios"), an innovative biotech company focused on the development of first-in-class therapies for autoimmune diseases and cancer, reported a US$8.8M Series A financing round with leading international healthcare investors Canaan and Australia’s Medical Research Commercialisation Fund managed by Brandon Capital ("MRCF") (Press release, Pathios Therapeutics, DEC 18, 2019, View Source [SID1234553270]).

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Pathios also announced the appointment of Stuart Hughes as Chief Executive Officer and Director. Formerly Senior Director and Head of Pharmacology at Vertex Pharmaceuticals (Europe) Limited, Stuart is seasoned in drug discovery and development, with a breadth of experience leading translational drug development programs across a range of therapeutic areas.

Tom McCarthy, Executive Chairman and Co-Founder, commented: "We established Pathios to capitalize on emerging scientific evidence that the pH sensing GPCR, GPR65, is a critical regulator of T-cells and tumour associated macrophages. We are proud of the recent progress we’ve made to expand the founding team and the acceleration of our drug discovery efforts following close collaboration with the team at Sygnature Discovery and their investment earlier this year. We are now on the verge of clearly defining the biological processes GPR65 controls, it’s genetic links to disease and how small molecules can modulate its signalling. As we push ahead, we are delighted to have additional support from such well-credentialed investors and to welcome Stuart to Pathios. He is a proven leader and strong communicator who possesses the skills and experience to execute on the Company’s strategy."

Pathios’ drug discovery programme is aimed at modulating the activity of GPR65. The company targets its signalling in cells of the immune system. Many pathological environments are characterized by abnormally acidic pH which signals to local immune cells leading to profound and unfavourable changes in their characteristics. A key mediator of these effects is GPR65 which is highly expressed on cells of both the adaptive and innate immune systems. Pathios is developing novel drugs to suppress the harmful signalling brought about by GPR65.

This drug target is characteristic of certain T helper 17 (Th17) cell populations which have been shown to contribute significantly to the pathology of autoimmune conditions, such as ankylosing spondylitis and psoriatic arthritis. In addition, recently published studies have demonstrated GPR65 drives tumour associated macrophages (TAM) to adopt a phenotype that supports cancer immune evasion.

Stuart Hughes, Chief Executive Officer of Pathios Therapeutics Limited, commented: "I am thrilled at the opportunity to lead Pathios Therapeutics at such an exciting time in the company’s journey. Pathios has an excellent foundation for exploiting the therapeutic potential of GPR65 in the immune system. I look forward to working with the team and building on the excellent science done so far to bring that to fruition. I am also delighted to see the company backed by such high-calibre investors, enabling us to accelerate our drug discovery efforts."

Chris Nave, Partner at Brandon Capital, commented: "Pathios represents a compelling opportunity to deliver first in class medicines that modulate a key pH-sensing GPCR in a pathological low pH environment. We are pleased to be working with Tom again after being one of the early investors in Spinifex. We are also pleased that our investment facilitates the ongoing collaboration between Pathios and Dr Jess Holien at Melbourne’s St Vincent’s Institute (SVI) of Medical Research and the Pathios team are exploring other collaborative opportunities with MRCF members given Australia’s internationally recognised track record in immunology and oncology translational research."

Brent Ahrens, General Partner at Canaan, added: "This is Canaan’s third time backing Tom – with his track record at Spinifex and Grey Wolf, it’s easy to see why. The addition of Stuart – with his significant experience as a drug discovery expert and leader – makes this opportunity even more appealing. The team is poised to develop first-in-class therapies in autoimmune disease and immuno-oncology. We are thrilled to be supporting this exceptional team as they execute an ambitious vision."

On December 18, 2019 The Jackson Laboratory (JAX) reported that it has received $2.5 million from The Mark Foundation for Cancer Research to study in mice the influence of host genetics on response to immunotherapy (Press release, The Mark Foundation For Cancer Research, DEC 18, 2019, View Source [SID1234553264]). The goal of this project is to generate insights that will empower future decisions about the best treatments for cancer patients based on their genetic backgrounds.

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Immunotherapy, which uses the body’s own immune system to fight cancer, is one of the most promising approaches to cancer treatment today, and expanding its effectiveness to a wider population of patients is a high priority for researchers across the globe.

The project, "Dissecting the Genetic Control of Response to Immune Checkpoint Inhibitors in Cancer," has major implications for how oncologists may be able to predict whether their patients will respond positively to immunotherapy before prescribing a treatment regimen.

A unique opportunity

Immunotherapy has resulted in some remarkable outcomes for patients whose cancers would have otherwise been fatal. Nonetheless, the overall efficacy rates for this class of treatment are not high, and many patients experience serious or even life-threatening side effects. The determination of which patients will respond well to immunotherapy is still uncertain. Probing factors that may influence response to immunotherapy, such as the personal genetics of each individual, tumor characteristics, and the cross-talk among these profiles is a critical step toward designing immune therapies that will have broader impact.

JAX President and CEO Edison T. Liu, MD and Associate Professor Laura Reinholdt, PhD, co-principal investigators of the study, will use genetically diverse JAX mouse models to untangle the relationship between genetics and response to immunotherapies.

"This research may one day allow doctors to use genetic sequencing to predict patient response to immunotherapy, as well as help scientists develop more effective anti-cancer drugs that fight tumors by activating an immune response," said Liu. "We are so grateful to The Mark Foundation for enabling this extraordinary opportunity, which we hope will have a significant impact on patients and the field of immunotherapy," said Liu.

The mission of The Mark Foundation for Cancer Research is to support scientists tackling the toughest challenges in cancer research. Multi-disciplinary groups such as the JAX team, which brings together experts in genetics, bioinformatics, mouse models, and immunology, are well positioned to take on these challenges. By funding this type of collaborative project, The Mark Foundation ensures that the right expertise is brought to bear on a substantial unmet need, ultimately accelerating cancer research to the benefit of patients.

"This project addresses critical limitations in cancer research. First, most mouse models for studying therapeutic response lack the genetic diversity that exists in the human population, often leading to disappointment when treatments that show promise in these models are deployed broadly in patients. Second, the biology of how genetics impact tumor response is not well understood due to a lack of adequate experimental systems for uncovering new knowledge", said Michele Cleary, PhD, CEO of The Mark Foundation. "Solving both of these issues requires the type of complex and nuanced work in mouse genetics for which JAX is world-renowned."

The power of genetic diversity

The grant to the Jackson Laboratory research team, which also includes Assistant Professor Chih-Hao "Lucas" Chang, PhD, Associate Research Scientist John P. Graham, PhD, Professor Karolina Palucka, MD, PhD, and Research Scientist Daniel Skelly, PhD, will examine four different tumor lines: a melanoma tumor, a triple-negative breast cancer tumor, and two types of colon cancer tumors. The tumor types were chosen to represent a wide range of responses to immunotherapy. For example, melanoma tumors tend to respond quite well to immunotherapy, whereas triple-negative breast cancer tumors typically do not.

The scientists will use JAX’s genetically diverse mouse strains in their studies, which will allow them to identify the genetic differences that underlie the variation in response to immunotherapy. Such an approach is inordinately difficult to achieve in human clinical trials.

"The increasing adoption of genetically diverse mice in biomedical research is really a paradigm shift driven by new technologies and biological resources, and by the recognition that an inbred mouse strain only represents one genome," said Reinholdt.

"This project is providing a unique opportunity to harness natural genetic variation in laboratory mice to more accurately model the biological complexity of cancer treatment response. The power of these genetically diverse mouse strains is that they facilitate genetic discovery and they provide tractable in vivo systems for dissecting molecular pathways, which are essential for the identification of biomarkers and potentially new therapeutic targets."

The research team plans to map the genetic differences found in the mice to specific genetic variants in humans. Ultimately, they hope that doctors will be able to test and determine a given individual’s likely response to immunotherapy to help guide the selection of a treatment regimen.

On December 18, 2019 The lOR Institute of Oncology Research reported that new grant awarded to the Tumor Biology and Experimental Therapeutics Group (Press release, The lOR Institute of Oncology Research, DEC 18, 2019, View Source [SID1234553216]).

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The project Nanoparticle-based delivery and combinatorial therapies for cancer funded by SNSF in the context of the European COST action on Cancer Nanomedicine (CA17140) aims at developing new nanoparticle-based medicine for precision therapy of advanced prostate cancer.

The project involves scientific partners in Turkey (Prof. Rana Sanyal, Department of Chemistry, Center for Life Sciences and Technologies Bogazici University, Istanbul, View Source) and in France (Maria Eugenia Riveiro, CSO Early Drug Development Group, www.e2dg.com).