On April 18, 2016 Kymab has announced a strategic collaboration with Heptares Therapeutics to discover, develop and commercialise novel antibody therapeutics targeting a number of G-protein-coupled receptors (GPCR) with an initial focus on immuno-oncology (Press release, Kymab, APR 18, 2016, View Source [SID1234537011]).

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GPCRs are widely expressed on cells of the innate and adaptive immune system and play key roles in modulating cell migration and recruitment to the tumour environment, activation, survival, proliferation and differentiation. GPCRs act at critical checkpoints that can be targeted by novel immunotherapy antibodies.

"GPCRs have long been intractable targets for antibody discovery resulting in dearth of products," said Dr Malcolm Weir, Chairman and CEO of Heptares, "We believe that our proven StaR technology can unlock this substantial opportunity, not just in immuno-oncology but also across other therapeutic areas where GPCR-targeted biologics could have a significant impact. By entering into strategic collaborations with companies with world-leading antibody discovery technologies, such as Kymab, we have the potential to discover, develop and commercialise a highly valuable pipeline of new biologic products."

Immuno-oncology is an exciting new area in the treatment of cancer where the body’s immune system is activated to produce an immune response targeted at tumour cells. Immunotherapy drugs are poised to revolutionise the way cancer is treated and a number of immunotherapy antibody treatments have recently been approved.

"Antibodies are important therapeutic agents for cancer and other indications," said Dr David Chiswell, Chairman and CEO of Kymab. "Our collaboration with Heptares will allow us to combine stable antigens based on multiple GPCR targets with our world class Kymouse platform which has unparalleled diversity and will therefore rapidly identify and yield highly selective potent human monoclonal antibodies for unmet medical needs."

Under the agreement, Heptares Therapeutics ("Heptares"), the wholly-owned subsidiary of Sosei Group Corporation (TSE Mothers Index: 4565), will apply its StaR platform to create stable antigens based on multiple GPCR targets chosen by the companies. Kymab will then use its Kymouse human antibody discovery platform to generate antibodies in response to immunisation with these antigens. The Kymouse platform will assure the highest probability of finding the best-in-class antibodies with highly attractive drug properties.

Promising leads will be progressed using the partners’ complementary skills, resources and development capabilities in order to bring innovative products into the clinic. Under the agreement, the companies will jointly conduct and share the costs of each antibody discovery and development programme.

On April 18, 2016 Heptares Therapeutics ("Heptares"), the wholly-owned subsidiary of Sosei Group Corporation (TSE Mothers Index: 4565), and Kymab Limited, a leading human monoclonal antibody biopharmaceutical company, reported that they have entered into a strategic collaboration to discover, develop and commercialise novel antibody therapeutics targeting a number of G protein-coupled receptors (GPCR) with an initial focus on immuno-oncology (Press release, Heptares, APR 18, 2016, View Source [SID:1234514761]).

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Immuno-oncology is an exciting new area in the treatment of cancer where the body’s immune system is activated to produce an immune response targeted at tumour cells. Immunotherapy drugs are poised to revolutionise the way cancer is treated and a number of immunotherapy antibody treatments have recently been approved. GPCRs are widely expressed on cells of the innate and adaptive immune system and play key roles in modulating cell migration and recruitment to the tumour environment, activation, survival, proliferation and differentiation. GPCRs act at critical checkpoints that can be targeted by novel immunotherapy antibodies.

Under the agreement, Heptares will apply its StaR platform to create stable antigens based on multiple GPCR targets chosen by the companies. Kymab will then use its Kymouse human antibody discovery platform to generate antibodies in response to immunisation with these antigens. The Kymouse platform will assure the highest probability of finding the best-in-class antibodies with highly attractive drug properties. Promising leads will be progressed using the partners’ complementary skills, resources and development capabilities in order to bring innovative products into the clinic. Under the agreement, the companies will jointly conduct and share the costs of each antibody discovery and development programme.

Malcolm Weir, Chairman and CEO of Heptares, said: "GPCRs have long been intractable targets for antibody discovery resulting in dearth of products. We believe that our proven StaR technology can unlock this substantial opportunity, not just in immuno-oncology but also across other therapeutic areas where GPCR-targeted biologics could have a significant impact. By entering into strategic collaborations with companies with world-leading antibody discovery technologies, such as Kymab, we have the potential to discover, develop and commercialise a highly valuable pipeline of new biologic products."

David Chiswell, CEO of Kymab, said: "Antibodies are important therapeutic agents for cancer and other indications. Our collaboration with Heptares will allow us to combine stable antigens based on multiple GPCR targets with our world-class Kymouse platform, which has unparalleled diversity and will therefore rapidly identify and yield highly selective potent human monoclonal antibodies for unmet medical needs."

On April 18, 2016 Mersana Therapeutics, Inc. reported that preclinical data for its new immunoconjugate product candidate, XMT-1536, demonstrated significant anti-cancer activity in non-small cell lung cancer (NSCLC) and ovarian cancer tumor models (Press release, Mersana Therapeutics, APR 18, 2016, View Source [SID:1234513852]). The data were presented today during a poster session at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA.

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XMT-1536 is a highly potent anti-sodium-dependent phosphate transport protein 2B (anti-NaPi2b) immunoconjugate comprised of an average of 15 auristatin molecules conjugated to XMT-1535, a novel humanized anti-NaPi2b antibody, via the Dolaflexin antibody-drug conjugate (ADC) platform. Dolaflexin is one of Mersana’s proprietary Fleximer immunoconjugate platforms.

"We are encouraged by the durable regressions XMT-1536 achieved in non-small cell lung cancer and ovarian cancer tumor models, as well as the excellent tolerability and pharmacokinetics in non-human primate exploratory toxicology studies," said Donald A. Bergstrom, MD, PhD, Chief Medical Officer of Mersana. "Based on these data, we are advancing XMT-1536 into IND-enabling studies for the treatment of patients with NaPi2b-expressing tumors."

The study evaluated XMT-1536 in non-squamous NSCLC and non-mucinous ovarian cancer tumor models, indications in which NaPi2b is highly expressed. XMT-1536 demonstrated significant efficacy in all four patient-derived xenograft models representative of the target patient populations. In three patient-derived models of NSCLC, including KRAS-mutant NSCLC, XMT-1536 induced tumor regressions after three weekly doses of 3 mg/kg. In an ovarian cancer xenograft model, XMT-1536 induced partial tumor regressions after a single dose of 3 mg/kg, and complete tumor regressions after a single dose of 5 mg/kg or three weekly doses of 3 mg/kg. XMT-1536 was well-tolerated with no evidence of bone marrow toxicity in non-human primates at up to seven times the dose associated with tumor regression in the mouse xenograft models.

"XMT-1536 further validates the ability of Mersana’s Fleximer platform to generate targeted therapies that have the potential to address unmet needs and improve outcomes for patients with cancer. While there have been recent advancements in the treatment of non-small cell lung cancer and ovarian cancer, there remains tremendous need to address the significant proportion of patients who do not derive full benefit from currently available treatments," said Anna Protopapas, President and Chief Executive Officer of Mersana. "We look forward to the continued development of this second product candidate in our growing pipeline of Fleximer-based immunoconjugate therapies, as we prepare to enter the clinic with XMT-1522 this year."

On April 18, 2016 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported a new set of preclinical data further validating the potential of its first-in-class anti-MICA/B antibody IPH4301 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans, Louisiana, USA (Press release, Innate Pharma, APR 18, 2016, View Source [SID:1234511087]).

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Poster #1491 reports that IPH4301, a humanized antibody, binds with high affinity to MICA/B and is a potent cytotoxic antibody, inducing direct tumor cell killing by ADCC. Moreover, an additional mode-of-action of the same antibody was revealed, whereby the antibody has the potential to overcome immunosuppression in tumors.

Among the highly immune-suppressive cell types in cancer are tumor-associated macrophages or myeloid-derived suppressor cells (MDSC), which can reduce NK and T cell activities. In vitro, IPH4301 could overcome immunosuppression by macrophages, restoring NK cell antibody-mediated killing to levels seen in the absence of suppressor macrophages. In addition, IPH4301 blocked MICA/B-induced down-modulation of NKG2D receptors on NK and CD8 T cells, thus disrupting a second immuno-suppressive mechanism. Finally, treatment with IPH4301 restored NK cell infiltration, prevented tumor growth and improved survival in different in vivo tumor models.

Nicolai Wagtmann, CSO of Innate Pharma, said: "We are enthusiastic about IPH4301 as a therapeutic candidate because of its dual mode of action, combining potent ADCC-mediated tumor killing with interesting immuno-modulating properties. The ability of IPH4301 to interfere with these immune-suppressive pathways, while at the same time retaining high direct ADCC potency, makes for a novel, unique proposition in the immune-oncology landscape. IND-enabling studies will start in 2016".

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CD123 is a subunit of the heterodimeric interleukin-3-receptor (IL-3R) which is widely expressed on human hematologic malignancies including acute myeloid leukemia (AML). In addition, CD123 can be found on the surface of B cell acute lymphoblastic leukemia (B-ALL), hairy cell leukemia, blastic plasmacytoid dendritic cell neoplasm (BPDCN), chronic myeloid leukemia (CML) and Hodgkin’s lymphoma.

Of these malignancies, we are currently investigating CD123 as a target for adoptive cellular immunotherapy in AML since high CD123 expression is associated with enhanced AML blast proliferation, increased resistance of blasts to apoptosis, and poor clinical prognosis.

Acute Myeloid Leukemia (AML), is a cancer of the myeloid line of blood cells characterized by rapid growth of abnormal white blood cells that accumulate in the bone marrow. AML is the most common form of acute leukemia. Although AML is a relatively rare disease there are approximately 20,000 new cases per year in the US and 10,000 deaths per year, accounting for approximately 1.8% of cancer deaths in the US (SEER). AML standard of care involves chemotherapy to induce remission followed by additional chemotherapy or hematopoietic stem cell transplant. Allogeneic stem cell transplantation is the preferred treatment route for AML following a second remission. It can lead to a 5-year disease free survival in 26% of patients. Unfortunately however, currently, only about half of relapsed patients are able to achieve a second remission with traditional chemotherapy agents. Patients who do not achieve a second remission are much less likely to benefit from transplantation and face a poor outcome.

The use of CAR-T immunotherapy in relapsed AML patients may offer the potential to achieve a complete or longer lasting remission. City of Hope developed CD123 targeted CAR-T cells designed to be both activated to proliferate and to kill CD123 expressing tumor cells. The therapy is designed to recognize and eliminate leukemic cells leading to remission in patients with relapsed or refractory AML and could serve as a bridge to potentially curative allogenic stem cell transplant. The manufacturing process genetically modifies T-cells isolated from peripheral blood mononuclear cells to express a CD123-specific, hinge–optimized, CD28 co-stimulatory domain expressing CAR as well as an EGFRt selection/safety marker. The last feature acts a safety switch to allow depletion of CAR-T cells in the patients if needed.

In collaboration with the COH, we have an on-going phase I clinical study to assess the anti-tumor activity and safety of administering CD123 targeted CAR-T cells and are currently treating patients. We will assess the T-cell persistence and determine the potential immunogenicity of the cells to determine a recommended phase II dose.