On April 17, 2018 Euronext Paris: FR0010331421 – IPH) reported that new preclinical data of the Company’s broad and innovative portfolio of next generation immunotherapies have been presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 14-18, in Chicago (Press release, Innate Pharma, APR 17, 2018, View Source [SID1234525405]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Eric Vivier, Chief Scientific Officer of Innate Pharma, said: "Innate Pharma has always been driven by innovation and we are very proud to present new preclinical data from our broad and innovative portfolio of next generation immunotherapies. These data not only underpin our ongoing clinical program but also highlight the next wave of immunotherapies in cancer."

Innate Pharma has presented four posters featuring new preclinical data at the Immune Checkpoints sessions on 16 April.

Monalizumab in combination with cetuximab:
Data (ID: 1690) demonstrates that squamous cell carcinoma of the head & neck (SCCHN) tumor cells are infiltrated by NK and CD8+ T cells expressing CD94/NKG2A and that these cancer cells express the natural ligand of NKG2A, HLA-E. Blockade of NKG2A potentiated cetuximab induced antibody-dependent cell-mediated cytotoxicity (ADCC) towards SCCHN cell lines. Overall, the data support the Company’s ongoing Phase I/II trial for the combination of monalizumab and cetuximab in recurrent and/or metastatic SCCHN for which first clinical activity data will be presented today at 1:00 PM Chicago time during the "Phase I/II, II, and III Trials in Progress" poster session.

Monalizumab in combination with durvalumab:
New preclinical data (ID: 2714) suggest the combination of monalizumab and durvalumab is a potent immunotherapy for solid tumors. Tumor infiltrating NK and CD8+ T cells expressing NKG2A and/or PD-1 are present in several cancer types.

Blocking both NKG2A/HLA-E and PD-1/PD-L1 pathways enhanced anti-tumor responses of NK and CD8+ T cells in vitro and in vivo in mice. Taken together, these data support the rationale for ongoing clinical trials investigating the monalizumab/durvalumab combination in various solid tumors
.
IPH52 and IPH53, targeting the adenosine pathway:
Additionally, preclinical data (ID: 2718) support the development of anti-CD39 (IPH52) and anti-CD73 (IPH53) neutralizing antibodies targeting the ATP/Adenosine immune checkpoint pathway for cancer immunotherapy, potentially in combination with chemotherapy or immune checkpoint blockade.
These antibodies potently inhibit the enzymatic activity of both the soluble and membrane-associated forms of their respective target enzymes. In vitro, both antibodies efficiently reverse adenosine-mediated T cell suppression in the presence of ATP. IPH52, a first-in-class CD39 blocking antibody, sustains high concentrations of extracellular ATP that promotes immune responses by enhancing dendritic cell (DC) activation and subsequent T cell proliferation. IPH53 is more potent in vitro than benchmark anti-CD73 antibodies currently under clinical development. Additionally, combining IPH52 and IPH53 lead to a strong reversion of immune cell inhibition in the presence of ATP. Humanized IPH52 and IPH53 are currently in preclinical development.

Siglec-9, a new checkpoint for cancer immunotherapy:
In another highlight, preclinical findings (ID: 2713) for a first-in-class antibody program targeting Siglec-9 were presented. Siglecs comprise a family of 15 members of sialic acid-binding receptors. Siglec-9 is an inhibitory receptor of the family that is expressed on a broad range of immune cells of both lymphoid and myeloid origin. Siglec-9 can interact with sialic acids expressed by tumors, leading to dampened immune cell functions. Thus, Siglec-9-sialic acid interaction disruption may promote anti-tumor immunity.
Data show that antibodies against Siglec-9 generated by Innate Pharma enhance NK cell cytotoxicity. This anti-tumor response is improved by the blockade of the immune checkpoint NKG2A. Further, data demonstrate that Siglec-9 is highly expressed on tumor-infiltrating myeloid cells and upregulated on T cells in cancer, suggesting a potential additional role as an inhibitory checkpoint agent.

On April 17, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for its anti-coagulation factor IXa/X humanized bispecific monoclonal antibody / coagulation factor VIII substitute, "HEMLIBRA" [US generic name: emicizumab-kxwh] for people with hemophilia A without factor VIII inhibitors (Press release, Chugai, APR 17, 2018, View Source [SID1234525404]). Development and distribution of the drug in the US is conducted by Genentech, a member of Roche Group.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are thrilled that HEMLIBRA has been granted its second Breakthrough Therapy Designation," said Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit, Dr. Yasushi Ito. "This will allow us to expedite potential delivery of this new therapy we created to people with hemophilia A without inhibitors in the US following the previous designation for inhibitors. We continue to work closely with Genentech to enable this line extension as soon as possible."

This designation is based on the global phase III HAVEN 3 (NCT02847637) study evaluating HEMLIBRA subcutaneous injection once a week and once every two weeks in people with hemophilia A (12 years of age or older) without inhibitors to factor VIII.

Hemophilia A is a disease presenting repeated severe bleeding symptoms. In this disease, the blood coagulation reaction does not proceed normally due to the deficiency or functional disorder of coagulation factor VIII. For people with hemophilia A without inhibitors, regular factor VIII replacement therapy has been widely used to prevent bleeding. HEMLIBRA is a bispecific monoclonal antibody, which was developed using Chugai’s proprietary antibody engineering technologies. The drug is designed to bind factor IXa and factor X. In doing so, HEMLIBRA provides the cofactor function of factor VIII in people with hemophilia A, who either lack or have impaired coagulation function of factor VIII1, 2). In the HAVEN 3 study, a statistically significant reduction in the frequency of bleeding episodes was observed with HEMLIBRA. With the convenience of subcutaneous administration and the lower frequency of administration, it is expected to be a new treatment option for hemophilia A.
This is the sixth Breakthrough Therapy Designation received for three drugs created by Chugai: ALECENSA (ALK-positive non-small cell lung cancer with disease progression on crizotinib, and first line treatment for ALK-positive non-small cell lung cancer), ACTEMRA (systemic sclerosis and giant cell arteritis), and HEMLIBRA (prophylactic treatment for patients 12 years or older with hemophilia A with factor VIII inhibitors).

Trademarks used or mentioned in this release are protected by law.
References
Kitazawa, et al. Nature Medicine 2012; 18(10): 1570
Sampei, et al. PLoS ONE 2013; 8: e57479
About Breakthrough Therapy
Breakthrough Therapy Designation was adopted as part of the FDA Safety and Innovation Act (FDASIA) enacted in July 2012 aiming at expediting the development and review of drugs for the treatment of severe or life-threatening diseases or symptoms. In order to grant Breakthrough Therapy Designation, preliminary clinical evidence is required demonstrating that the drug may have substantial improvement on at least one clinically significant endpoint over existing therapies. Breakthrough Therapy Designation includes the features of a Fast Track designation, with the addition of intensive guidance on efficient drug development as well organizational commitment from FDA.
Main approval status of the drug

US: In November 2017, the drug (US product name: HEMLIBRA; Genentech) was approved by the U.S. Food and Drug Administration and was marketed for "routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors."

EU: In Europe, the drug (EU product name: HEMLIBRA; Roche) obtained regulatory approval from the European Commission and was marketed for routine prophylaxis of bleeding episodes in people with hemophilia A with factor VIII inhibitors in February 2018.
Japan: The Ministry of Health, Labour and Welfare has approved HEMLIBRA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with congenital factor VIII deficiency (hemophilia A) with factor VIII inhibitors in March 2018.
About the results of HAVEN 3 study
Press release issued on November 20, 2017
View Source

On April 16, 2018 Taiho Pharmaceutical Co., Ltd., a Japanese R&D-driven specialty pharma focused on oncology and Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, reproted that they are collaborating on the development of an investigational highly-selective RET inhibitor TAS0286/HM05, being evaluated in non-small cell lung cancer and other carcinomas (Press release, Helsinn, APR 16, 2018, View Source [SID1234561171]). Preliminary data regarding TAS0286/HM05 is being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting in Chicago, Illinois, U.S.A. Abstracts of the presentations are available at: View Source!/4562/presentation/6785

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In in-vitro preclinical studies, TAS0286/HM05 inhibited the proliferation of various RET fusions and RET-activating mutations positive cells as well as in in-vivo preclinical studies, TAS0286/HM05 was shown to significantly inhibit the growth of tumors harboring various RET fusions and activating mutations at a range of 20 to 100 mg/kg/day without any body weight loss. The antitumor efficacy of TAS0286/HM05 was more potent than pre-existing multikinase inhibitors at their maximum tolerated dose. Primary data in mice studies has shown an effect in tumor growth, providing an induced tumor regression of 40% within 15 days. This study is being presented as a poster on Tuesday, April 17 from 1:00 PM to 5:00 PM CST in Poster Section 36, Poster Board Number 13 (Abstract No. 4784).

"Preliminary data for TAS0286/HM05 suggests it may be a potential agent for future clinical development in patients with RET gene abnormalities," Sergio Cantoreggi, Helsinn Group Chief Scientific Officer commented. "Helsinn and Taiho Pharmaceutical have collaborated over many years on a number of programs and we are delighted to be able to present this promising preclinical data, and we look forward to further collaboration."

"Over the years, Taiho Pharmaceutical has collaborated with Helsinn as an excellent partner in the development and marketing of new drugs. I am excited about the new collaboration with Helsinn on the selective RET inhibitor that was discovered by the Taiho Tsukuba Research Center. I look forward to the success of the program and the strengthening of our partnership." Teruhiro Utsugi, Taiho Managing Director commented.

TAS0286/HM05 was discovered by Taiho Pharmaceutical and it will now be jointly developed by Helsinn and Taiho Pharmaceutical. TAS0286/HM05 is an investigational agent and is not approved for commercial use in any country.

On April 16, 2018 Oncoceutics, Inc. reported that the first patient has been treated in a Phase I/II clinical trial of ONC201 in combination with ixazomib and dexamethasone in relapsed and/or refractory multiple myeloma (Press release, Oncoceutics, APR 16, 2018, View Source [SID1234558369]). The trial, led by Ajai Chari, MD, Associate Professor at the Icahn School of Medicine at Mount Sinai, is entitled "A Phase I/II Study of the Addition of Ixazomib to ONC201 and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma" (NCT03492138) and seeks to combine two oral medications that have shown synergy against multiple myeloma in preclinical models. The study will enroll up to 36 adult patients and will evaluate the safety and tolerability of ONC201 in combination with ixazomib and dexamethasone in Phase I and determine the two-month disease control rate as the primary endpoint of Phase II.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

While Oncoceutics is currently focused on clinical trials of ONC201 in high-grade gliomas as its lead indication, the company continues to advance a number of clinical programs in B cell malignancies because they have shown some of the highest sensitivity against ONC201 in pre-clinical models. Oncoceutics currently has two programs in multiple myeloma: "Oral ONC201 in Relapsed/Refractory Multiple Myeloma" (NCT02863991) and the combination trial with ixazomib described above.

Multiple myeloma is highly sensitive to proteasome inhibitors that activate the integrated stress response, the same pathway activated by ONC201 treatment through unique triggers. ONC201 synergizes with proteasome inhibitors since they converge on some of the same downstream effects as ONC201 even though they use distinct triggers in tumor cells. Based on this rationale, which is supported by published preclinical studies (Prabhu et al, Cell Cycle 2018; Tu et al, Neoplasia 2017), this clinical trial will test the combination of ONC201 with ixazomib and dexamethasone. Ixazomib, which goes by brand name NINLARO, is an oral proteasome inhibitor developed by Takeda Pharmaceutical Company. It is FDA approved in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In addition to the U.S., NINLARO is approved in more than 50 countries.

"We are excited to have the opportunity to test these two oral agents that have demonstrated efficacy against multiple myeloma in pre-clinical settings to provide therapies to patients with refractory/relapsed multiple myeloma that are in need of novel therapies," said Ajai Chari, Associate Professor, Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mt. Sinai.

On April 16, 2018 Nordic Nanovector ASA (OSE: NANO) reported that a poster reporting the anti-tumour effect of Humalutin (177Lu-conjugated humanized anti-CD37 antibody, 177Lu-NNV003) in preclinical models of non-Hodgkin’s lymphoma (NHL) was presented yesterday at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in Chicago, USA (Press release, Nordic Nanovector, APR 16, 2018, View Source [SID1234553507]). The company previously announced the publication of the poster abstract (abstract 848) on 15 March 2018.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster was entitled "In vitro and in vivo evaluation of the beta-emitting lutetium-177 labeled anti-CD37 antibody radionuclide conjugate 177Lu-NNV003 in DLBCL, CLL and MCL models," and showed that:

In tumour cell lines:

• The unlabelled anti-CD37 antibody (NNV003) kills tumour cells mainly through an immunological process called antibody dependent cellular cytotoxicity

• Humalutin (177Lu-NNV003) was found to inhibit tumour cell growth.

In preclinical lymphoma models:

• Humalutin has shown significant tumour uptake and demonstrated an anti-tumour effect in all three NHL models (mantle cell lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukaemia).