On July 12, 2018 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), ("Onxeo" or "the Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs in oncology, in particular against rare or resistant cancers, reported new positive results from preclinical studies of AsiDNA, its first-in-class DNA Repair inhibitor, in combination with PARP inhibitors (PARPi) (Press release, Onxeo, JUL 12, 2018, View Source [SID1234527668]). The results of these extensive studies with different PARPi point to the ability of AsiDNA to prevent the occurrence of resistance and even to reverse the acquired resistance of the tumor cell after PARPi treatments. Furthermore, they show that the combination has a strong synergistic anti-tumor activity in in vitro and in vivo models of solid tumors resistant to PARPi (HR proficient). Together with the preliminary data on the activity and safety of AsiDNA expected in Q4 2018 from the DRIIV-1 clinical trial, these results support clinical development of AsiDNA in combination with PARP inhibitors, which should start from year-end 2018.

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Judith Greciet, Chief Executive Officer of Onxeo, said: "Onxeo is conducting an ambitious development program for AsiDNA, notably translational, in combination with various anti-cancer agents in order to provide strategic information aimed at determining the indications and combinations to target in further clinical development as soon as the first results from DRIIV-1 are available. Assessing the combination of AsiDNA with PARPi is a priority, as their mechanisms of action are very complementary in indications with high unmet medical needs. Sales for the PARPi class are already substantial in ovarian cancer and are expected to increase markedly in the near-term as products gain access to multiple additional oncology indications. Our recent studies indicate that AsiDNA in combination with PARPi could enable PARPi to overcome the requirement of a genetic mutation such as BRCA-, and show a strong synergistic activity versus PARPi alone. Moreover, the combination appears to both prevent the occurrence of resistance to PARPi and reverse the acquired resistance, which may considerably expand treatment duration with PARPi. A treatment combining AsiDNA and PARPi could therefore significantly broaden the patient population eligible to PARPi and improve their efficacy, which is of great interest to the scientific community, the pharmaceutical industry and the patients for its potential to address resistant cancers."

AsiDNA is a first-in-class DNA repair inhibitor in the field of DNA Damage Response (DDR) that mimics double-stranded DNA breaks in tumor cells, activating repair pathways, diverting repair enzymes from the target and finally depleting the cell through a unique mechanism of agonist and decoy.

Data show that in in vitro models of HR proficient TNBC (triple negative breast cancer) and SCLC (small cell lung cancer), AsiDNA maintains PARP1 expression, the repair enzyme inhibited by PARP inhibitors, and abrogates the occurrence of resistance to PARPi, including in models of cancers resistant to PARPi. Down regulation of the PARP1 enzyme is one of the mechanisms that supports the occurrence of resistance to PARPi inhibitors1. As AsiDNA hyper-activates repair enzymes, an up regulation of PARP1 expression following treatment with AsiDNA or with AsiDNA associated to PARPi support the use of AsiDNA to maintain the sensitivity to PARPi treatment.

Furthermore, combination treatment of olaparib with AsiDNA more than doubles the complete response rate observed with olaparib alone (71% vs. 33%) in an in vivo model of HR proficient TNBC model and inhibits tumor growth in a humanized Patient-Derived Xenograft (PDX) mice model of ovarian cancer resistant to olaparib. PDX models are considered highly predictive of clinical behavior2.

The Company will submit the detailed results of these preclinical studies to leading peer-reviewed publications and international scientific conferences.

Francoise Bono, Chief Scientific Officer of Onxeo, concluded: "These most recent data validate our disruptive approach to DNA-targeting and confirm the broad opportunities for our lead molecule thanks to its unique mechanism of action. Our team has built an extremely solid body of preclinical evidence, both in-vitro and in highly predictive humanized in-vivo models, which shows the potential of AsiDNA to reverse the resistance to PARP inhibitors and the strong synergy of their combination. This is the first part of our extensive translational plan which aims at confirming the full potential of AsiDNA in combination with other anticancer agents such as chemotherapies or epigenetic compounds, including belinostat. Additional data on these other possible combinations will be available after the summer to further inform the clinical development of AsiDNA in combinations offering the potential for significant therapeutic improvement."

On July 12, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported that it has entered into a research collaboration and exclusive license agreement with privately owned Immatics Biotechnologies GmbH (Immatics), to discover and develop next-generation bispecific immunotherapies to target multiple cancer indications (Press release, Genmab, JUL 12, 2018, View Source [SID1234527670]). The deal strengthens Genmab’s position in immuno-oncology by combining Genmab’s proprietary technologies and antibody know-how with Immatics’ XPRESIDENT targets and T-cell receptor (TCR) capabilities. Genmab will receive an exclusive license to three proprietary targets from Immatics, with an option to license up to two additional targets at predetermined economics. The companies will conduct joint research, funded by Genmab, on multiple antibody and/or TCR-based bispecific therapeutic product concepts.

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Genmab may elect to progress any resulting product candidates, and will be responsible for development, manufacturing and worldwide commercialization. For any products that are commercialized by Genmab, Immatics will have an option to limited co-promotion efforts in selected countries in the EU.

"This collaboration with Immatics gives us the opportunity to combine our unique technologies and expertise to create differentiated novel next-generation therapies. We very much look forward to this exciting partnership in the field of cancer immunotherapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Carsten Reinhardt, M.D., Ph.D., Chief Medical Officer and Managing Director of Immatics, commented: "We are very pleased to join forces with one of the world-leading biotechnology companies to develop and advance novel and highly active cancer therapeutics. This collaboration underpins Immatics’ leadership in intracellular tumor target identification and T-cell receptor engineering." Dr. Reinhardt further said: "Our bispecific TCR technology exhibits exceptional potency and favourable pharmacokinetic properties by combining Immatics’ proprietary T-cell engaging format with our high-affinity and highly specific T-cell receptors as reported at AACR (Free AACR Whitepaper) 20181."

Under the terms of the agreement, Genmab will pay Immatics an upfront fee of USD 54 million and Immatics is eligible to receive up to USD 550 million in development, regulatory and commercial milestone payments for each product, as well as tiered royalties on net sales.

Today’s news does not impact Genmab’s 2018 Financial Guidance.

On July 12, 2018 ImmunoGen, Inc., (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that Company will host a conference call at 8:00 a.m. ET on Friday, July 27, 2018 to discuss its second quarter operating results (Press release, ImmunoGen, JUL 12, 2018, View Source [SID1234527673]). Management will also provide a brief update on the business.

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Conference Call Information
To access the live call by phone, dial 719-785-1753; the conference ID is 2275763. The call may also be accessed through the Investors section of the Company’s website, www.immunogen.com. Following the webcast, a replay of the call will be available at the same location through August 10, 2018.

On July 12, 2018 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205), a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer (the "Company"), reported its unaudited revenues for the second quarter of 2018 (Press release, Nanobiotix, JUL, 12, View Source [SID1234527674]).

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Activity and results during the second quarter of 2018

The Company generated €73k during the second quarter of 2018, which is fully in line with the Company’s
expectations. Most of the revenue was generated from services that Nanobiotix crossed-charged to its partners as per its operational activities.

In April, Nanobiotix presented preclinical data showing that NBTXR3 nanoparticles can activate the cGAS-STING
pathway at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in Chicago, Illinois, USA (April
14-18, 2018). These observations support the rationale for using NBTXR3 with radiation therapy in combination with
immunotherapeutic agents and/or STING agonist to transform tumors into an in-situ cancer vaccine.

Nanobiotix also announced that it will cooperate with The University of Texas MD Anderson Cancer Center, Houston
TX, USA, to run immunotherapeutic pre-clinical research in lung cancer, combining NBTXR3 and Nivolumab. 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). Nanobiotix reported that it has been selected to enter Euronext’s Tech40 label, recognizing the best performing Tech SMEs listed on Euronext markets.

In May, Nanobiotix announced that it is launching a research collaboration with Weill Cornell Medicine to begin
nonclinical studies to evaluate the impact of NBTXR3 on cGAS-STING pathway in mammary cancers. The research
collaboration between Weill Cornell Medicine, based in New York City, and Nanobiotix will be conducted over the
course of one year, with the goal of continuing the exploration of the role of NBTXR3 in Immuno-Oncology.
In June, Nanobiotix announced positive phase II/III topline data in Soft Tissue Sarcoma with NBTXR3. The trial achieved its primary endpoint of pathological Complete Response Rate and its secondary endpoint in operability (R0 rate). NBTXR3 demonstrated significant superiority and clinical benefits for patients compared to the standard of care. The safety profile was confirmed. This randomized trial validated the first-in-class mode of action of NBTXR3.

The positive results from this study support and further validate the Company’s European regulatory strategy of the
previously submitted CE marking application in soft tissue sarcoma. The Company will submit the new data as a
supplement to the European Notified Body in a timely manner.

The Company will present the results at an upcoming international medical conference.
The clinical validation of NBTXR3’s physical mode of action in a very heterogeneous and hard-to-treat disease
strengthens the universal profile of the product and confirms the development strategy in multiple indications.
Currently, the Company is evaluating NBTXR3 in seven clinical trials with a focus on head and neck cancers and
Immuno-Oncology programs.

On July 11, 2018 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that the randomized, Phase 3 TOURMALINE-MM3 study met its primary endpoint, demonstrating single-agent oral NINLARO (ixazomib) as a maintenance therapy resulted in a statistically significant improvement in progression-free survival (PFS) versus placebo (Press release, Takeda, JUL 11, 2018, View Source [SID1234527655]). The trial evaluated the effect of NINLARO as a maintenance therapy in adult patients diagnosed with multiple myeloma who responded to high-dose therapy (HDT) and autologous stem cell transplant (ASCT). Takeda plans to submit data from the trial to regulatory agencies around the world. NINLARO is currently not approved as a maintenance therapy for multiple myeloma following ASCT.

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"Within the maintenance setting, it is critical that we find agents that are efficacious, tolerable and convenient," said Jesús Gomez Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. "The results of the TOURMALINE-MM3 trial represent an important step toward the goal of expanding the use of NINLARO as a maintenance therapy. This is the first and only Phase 3 placebo-controlled study evaluating a proteasome inhibitor in this setting and we look forward to discussions with Health Authorities around the world."

There were no new safety signals found in TOURMALINE-MM3. The safety profile of NINLARO in the maintenance setting is consistent with previously reported results of single-agent NINLARO use.

Full data results will be submitted for presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December.

About the TOURMALINE-MM3 Trial

TOURMALINE-MM3 is a randomized, placebo-controlled, double-blind Phase 3 study of 656 patients, designed to determine the effect of NINLARO (ixazomib) maintenance therapy on progression-free survival (PFS), compared to placebo, in participants with multiple myeloma who have had a response (complete response [CR], very good partial response [VGPR], or partial response [PR]) to induction therapy followed by high-dose therapy (HDT) and autologous stem cell transplant (ASCT). The primary endpoint is progression-free survival (PFS). A key secondary endpoint includes overall survival (OS). For additional information: View Source

About NINLARO (ixazomib) capsules

NINLARO (ixazomib) is an oral proteasome inhibitor which is also being studied across the continuum of multiple myeloma treatment settings as well as systemic light-chain (AL) amyloidosis. It was the first oral proteasome inhibitor to enter Phase 3 clinical trials and to receive approval. NINLARO was approved by the U.S. Food and Drug Administration (FDA) in November 2015 following a priority review and by the European Commission in November 2016. In the U.S. and Europe, NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. NINLARO has received marketing authorization by regulatory authorities in more than 55 countries.

Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory systemic light-chain (AL) amyloidosis, a related ultra orphan disease, in 2014. The Japanese Ministry of Health, Labour and Welfare granted Orphan Drug designation to ixazomib in 2016.

The comprehensive ixazomib clinical development program, TOURMALINE, includes a total of six ongoing pivotal trials – five, which together are investigating every major multiple myeloma patient population, and one in light-chain amyloidosis:

TOURMALINE-MM1, investigating ixazomib vs. placebo in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
TOURMALINE-MM2, investigating ixazomib vs. placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)
TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT; this study is currently enrolling
TOURMALINE-MM5, investigating ixazomib plus dexamethasone vs. pomalidomide plus dexamethasone in patients with relapsed and/or refractory multiple myeloma who have become resistant to lenalidomide
TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis; this study is currently enrolling
For more information about actively enrolling Phase 3 studies please visit: View Source

In addition to the TOURMALINE program, ixazomib is being evaluated in multiple therapeutic combinations for various patient populations in investigator initiated studies globally.

NINLARO (ixazomib) capsules: Global Important Safety Information

SPECIAL WARNINGS AND PRECAUTIONS
Thrombocytopenia has been reported with NINLARO (28% vs. 14% in the NINLARO and placebo regimens, respectively) with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle. It did not result in an increase in hemorrhagic events or platelet transfusions. Monitor platelet counts at least monthly during treatment with NINLARO and consider more frequent monitoring during the first three cycles. Manage with dose modifications and platelet transfusions as per standard medical guidelines.

Gastrointestinal toxicities have been reported in the NINLARO and placebo regimens respectively, such as diarrhea (42% vs. 36%), constipation (34% vs. 25%), nausea (26% vs. 21%), and vomiting (22% vs. 11%), occasionally requiring use of antiemetic and anti-diarrheal medications, and supportive care.

Peripheral neuropathy was reported with NINLARO (28% vs. 21% in the NINLARO and placebo regimens, respectively). The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.

Peripheral edema was reported with NINLARO (25% vs. 18% in the NINLARO and placebo regimens, respectively). Evaluate patients for underlying causes and provide supportive care, as necessary. Adjust the dose of dexamethasone per its prescribing information or the dose of NINLARO for severe symptoms.

Cutaneous reactions occurred in 19% of patients in the NINLARO regimen compared to 11% of patients in the placebo regimen. The most common type of rash reported in both regimens was maculo-papular and macular rash. Manage rash with supportive care, dose modification or discontinuation.

Hepatotoxicity, drug-induced liver injury, hepatocellular injury, hepatic steatosis, and hepatitis cholestatic have been uncommonly reported with NINLARO. Monitor hepatic enzymes regularly and adjust dose for Grade 3 or 4 symptoms.

Pregnancy- NINLARO can cause fetal harm. Advise male and females patients of reproductive potential to use contraceptive measures during treatment and for an additional 90 days after the final dose of NINLARO. Women of childbearing potential should avoid becoming pregnant while taking NINLARO due to potential hazard to the fetus. Women using hormonal contraceptives should use an additional barrier method of contraception.

Lactation- It is not known whether NINLARO or its metabolites are excreted in human milk. There could be potential adverse events in nursing infants and therefore breastfeeding should be discontinued.

SPECIAL PATIENT POPULATIONS
Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.

Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease (ESRD) requiring dialysis. NINLARO is not dialyzable and, therefore, can be administered without regard to the timing of dialysis.

DRUG INTERACTIONS
Co-administration of strong CYP3A inducers with NINLARO is not recommended.

ADVERSE REACTIONS
The most frequently reported adverse reactions (≥ 20%) in the NINLARO regimen, and greater than in the placebo regimen, were diarrhea (42% vs. 36%), constipation (34% vs. 25%), thrombocytopenia (28% vs. 14%), peripheral neuropathy (28% vs. 21%), nausea (26% vs. 21%), peripheral edema (25% vs. 18%), vomiting (22% vs. 11%), and back pain (21% vs. 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in ≤ 1% of patients in the NINLARO regimen.