On June 4, 2018 Euronext Paris: FR0010331421 – IPH) reported updated preliminary clinical data from an ongoing Phase I dose escalation and expansion study evaluating the safety and efficacy of the combination of monalizumab, a first-in-class monoclonal antibody targeting NK and T cell checkpoint receptor NKG2A, with durvalumab in patients with recurrent/metastatic microsatellite-stable colorectal cancer (MSS-CRC) (Press release, Innate Pharma, JUN 4, 2018, View Source [SID1234527252]). This trial is being conducted by MedImmune, AstraZeneca’s global biologics research and development arm, through a co-development and commercialization agreement.

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In a poster presentation made at the Gastrointestinal (Colorectal) Cancer session on Sunday, June 3 2018, during the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the combination of monalizumab and durvalumab showed encouraging anti-tumor activity in this difficult-to-treat patient subset.

"The preliminary data so far suggest that the combination of monalizumab and durvalumab may hold promise in some patients with MSS-CRC, a population historically unresponsive to PD-1/L1 therapy", said study investigator Neil H. Segal, MD., PhD., medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Pierre Dodion, Chief Medical Officer at Innate Pharma, added: "We are encouraged by the preliminary results from the ongoing trial observed in a heavily pretreated MSS-CRC patient population. These data have prompted our partner AstraZeneca/MedImmune to further expand the study with additional patient cohorts to explore the novel combination of this first-in-class antibody, monalizumab, with durvalumab on top of current standard of care therapies in patients with less heavily pretreated disease".

Key findings from the MSS-CRC expansion cohort:

Updated preliminary clinical data on the expansion cohort of microsatellite-stable colorectal cancer patients (MSS-CRC) presented at ASCO (Free ASCO Whitepaper) are based on the cut-off date of April 23, 2018. Forty patients are evaluable for safety and 39, for efficacy. Thirty five (88%) patients had 2 or more prior lines of therapy for recurrent/metastatic disease. Efficacy data show an overall response rate (ORR) of 8%, with confirmed partial response in 3 patients (8%) and stable disease (SD) in 11 patients (28%), including 3 SD patients with tumor reduction who continued therapy for >200 days. The median duration of response was 16.1 weeks at the cut-off date. Data demonstrated a disease control rate (DCR) of 31% at 16 weeks.

On June 4, 2018 ENTEROME SA, a clinical-stage biotechnology company pioneering innovative therapies to treat microbiome-associated diseases with a focus on inflammatory bowel diseases (IBD) and immuno-oncology (IO) indications, reported that it will attend the Jefferies 2018 Global Healthcare Conference (Press release, Enterome, JUN 4, 2018, View Source [SID1234527116]). The conference will be held in New York, June 5-8 and features an extensive range of public and private healthcare companies across the Biopharmaceuticals, Life Sciences, Healthcare Services, Healthcare IT and Medical Technology sectors. It hosted over 2,600 attendees in 2017.

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On June 4, 2018 Array BioPharma Inc. (NASDAQ: ARRY) reported updated results from the Phase 3 COLUMBUS trial in BRAF-mutant advanced melanoma (Press release, Array BioPharma, JUN 4, 2018, View Source [SID1234527132]). The results showed median overall survival (mOS) was 33.6 months for patients treated with the combination of encorafenib and binimetinib compared to 16.9 months for patients treated with vemurafenib as a monotherapy. The combination reduced the risk of death compared to treatment with vemurafenib alone [hazard ratio (HR) of 0.61, [95% CI 0.47, 0.79, p <0.0001]. The observed efficacy of vemurafenib in the control arm is also consistent with historical data, providing an additional benchmark for validating the patient population and results observed in COLUMBUS. [1, 2] Further, the two-year OS with combination therapy was 58%. These results will be part of an oral presentation today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, Illinois and have been selected for the "Best of ASCO (Free ASCO Whitepaper)" program.

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Importantly, the presentation will include data showing limited use of post-trial immunotherapy, which is consistent with other published pivotal trials of BRAF and MEK-inhibitors in BRAF-mutant advanced melanoma. [1, 3]

"The data presented today at ASCO (Free ASCO Whitepaper) demonstrate that the use of subsequent immunotherapies was consistent across treatment groups, indicating that these subsequent treatments are unlikely to have contributed to the observed differences in survival," said Keith T. Flaherty, M.D., Director of the Termeer Center for Targeted Therapy, Massachusetts General Hospital Cancer Center and Professor of Medicine, Harvard Medical School. "This further suggests encorafenib and binimetinib could be a promising new treatment option for patients with BRAF-mutant advanced melanoma."

Additionally, the updated median progression-free survival (mPFS) results for patients treated with the combination of encorafenib and binimetinib remained consistent with what was previously reported at 14.9 months versus 7.3 months for patients treated with vemurafenib [HR= 0.51, 95% CI 0.39-0.67; p<0.0001].

As previously reported, the combination of encorafenib and binimetinib was generally well-tolerated. Grade 3/4 adverse events (AEs) that occurred in more than 5% of patients receiving the combination were increased gamma-glutamyltransferase (GGT) (9%), increased blood creatine phosphokinase (CK) (7%) and hypertension (6%). The incidence of selected any grade AEs of special interest, defined based on toxicities commonly associated with commercially available BRAF+MEK-inhibitor treatments for patients receiving the combination of encorafenib and binimetinib included: rash (22%), serous retinopathy including retinal pigment epithelial detachment (20%), pyrexia (18%) and photosensitivity (5%). Full safety results of COLUMBUS Part 1 were published in The Lancet Oncology.

A PDF of the ASCO (Free ASCO Whitepaper) COLUMBUS presentation will be available on Array’s website.

In the COLUMBUS trial, eligible patients were randomized 1:1:1 to receive the combination of encorafenib, 450 mg daily, plus binimetinib, 45 mg twice daily, encorafenib 300 mg daily as a monotherapy, or vemurafenib 960 mg twice daily as a monotherapy.

Data from Array’s partnered programs with AstraZeneca, Genentech and Loxo Oncology were also presented on the Array-invented molecules selumetinib, ipatasertib and LOXO-292, respectively.

Array will host an encore webcast presentation of the COLUMBUS trial data.

Encore Webcast:
Presenter: Keith T. Flaherty, M.D.
Date: Monday, June 4, 2018
Time: 11:15 a.m. Central Time (12:15 p.m. Eastern Time)
Toll-Free: (844) 464-3927
Toll: (765) 507-2598
Pass Code: 9615719

Webcast, including replay and conference call slides: View Source

About Melanoma
Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [4, 5] There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma. [4, 6, 7, 8]

About COLUMBUS
The COLUMBUS trial (NCT01909453) is a two-part, international, randomized, open label Phase 3 trial evaluating the efficacy and safety of the combination of encorafenib and binimetinib compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial. Patients were randomized into two parts:

In Part 1, 577 patients were randomized 1:1:1 to receive the combination of encorafenib 450 mg daily and binimetinib 45 mg twice daily (COMBO450), encorafenib, 300 mg daily alone (ENCO 300), or vemurafenib, 960 mg twice daily alone. The dose of encorafenib in the combination arm is 50% higher than the single agent maximum tolerated dose of 300 mg. A higher dose of encorafenib was possible due to improved tolerability when combined with binimetinib. The primary endpoint for the COLUMBUS trial was an mPFS comparison of the COMBO450 arm versus vemurafenib. mPFS is determined based on tumor assessment (RECIST version 1.1 criteria) by a Blinded Independent Central Review (BICR). Secondary endpoints include a comparison of the mPFS of COMBO450 arm to that of ENCO300 and a comparison of overall survival (OS) in patients treated in the COMBO450 arm to that of vemurafenib alone. Results from Part 1 of the COLUMBUS trial, previously published in The Lancet Oncology May 2018, showed that COMBO450 more than doubled mPFS in patients with advanced BRAF-mutant melanoma, with a mPFS of 14.9 months compared with 7.3 months observed with vemurafenib [HR 0.54, (95% CI 0.41-0.71, p<0.0001)]. In the secondary mPFS comparison of COMBO450 to ENCO300, ENCO300 demonstrated a mPFS of 9.6 months [HR 0.75, (95% CI 0.56-1.00, p=0.051)].

In Part 2, 344 patients were randomized 3:1 to receive encorafenib 300 mg daily plus binimetinib 45 mg twice daily (COMBO300) or ENCO300. Part 2 was designed to provide additional data to help evaluate the contribution of binimetinib to the combination of encorafenib and binimetinib.
As the secondary endpoint comparison of mPFS between the COMBO450 arm and ENCO300 arm in Part 1 did not achieve statistical significance, the protocol specified analysis of OS is descriptive.

About Encorafenib and Binimetinib
BRAF and MEK are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma and colorectal cancer. Encorafenib is a late-stage small molecule BRAF inhibitor and binimetinib is a late-stage small molecule MEK inhibitor, both of which target key enzymes in this pathway. Encorafenib and binimetinib are being studied in clinical trials in advanced cancer patients, including the Phase 3 COLUMBUS trial and the Phase 3 BEACON CRC trial.

Array BioPharma has exclusive rights to encorafenib and binimetinib in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America. Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

On June 4, 2018 NewLink Genetics Corporation (NASDAQ:NLNK) reported that data from two Phase 2 studies of indoximod, used in combination with other agents, were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, NewLink Genetics, JUN 4, 2018, View Source [SID1234527148]).

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"Our data in advanced melanoma suggest that indoximod in combination with checkpoint blockade shows encouraging response rates potentially in both PD-L1 positive and negative patients," said Charles J. Link, Jr, MD, Chairman and Chief Executive Officer. "We wish to thank the patients and their caregivers who participated in both of these studies."

Indoximod in combination with checkpoint inhibition in advanced melanoma
Results from a single-arm Phase 2 study of indoximod in combination with checkpoint inhibitors for patients with advanced melanoma were presented today by Yousef Zakharia, MD, Assistant Professor of Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation at the University of Iowa and Holden Comprehensive Cancer Center.

In this study, of 102 total patients enrolled, 101 patients with advanced melanoma were treated with indoximod plus standard-of-care checkpoint inhibition as approved for melanoma. 70 patients with cutaneous or mucosal melanoma were treated with pembrolizumab plus indoximod and had an on-treatment imaging, meeting the per-protocol, pre-specified definition of evaluable for efficacy. Of the remaining 32 patients, 15 had uveal melanoma, 4 received ipilimumab, 4 received nivolumab, and one patient was never treated. In addition, 8 patients came off study prior to the first on-treatment imaging study. The full data set, including the expanded biopsy cohort, is provided on the company’s website in the "Posters & Presentations" section under the "Investors & Media" tab.
Key findings from the 70 evaluable for efficacy patients presented from the study include:
–
ORR for combination therapy of 56%
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CR of 19%
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Median PFS of 12.4 months
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PD-L1 ≥ 1% staining of 54% (22/41 patients with archival tissue)
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ORR by PD-L1 status
◦
PD-L1 (+) patients: ORR of 77%
◦
PD-L1 (-) patients: ORR of 42%
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Combination was well tolerated

Indoximod in combination with chemotherapy in metastatic pancreatic cancer
Results from a Phase 2 study of indoximod plus chemotherapy for patients with metastatic pancreatic cancer were presented at ASCO (Free ASCO Whitepaper) by Nathan Bahary, MD, PhD, Associate Professor in the Division of Oncology and Medical Director of the Pancreatic Cancer Program at the University of Pittsburgh Medical Center. Key findings from this study show that the combination was well tolerated with a median Overall Survival (mOS) of 10.9 months and an Overall Response Rate (ORR) of 46.1%. Although the study did not meet the prespecified primary goal of a 30% decrease in the risk of death compared with historical controls, the combination demonstrated potentially promising activity with an immunologic correlation for response to therapy. These data may be found on the company’s website in the "Posters & Presentations" section under the "Investors & Media" tab.

Exhibit 99.1

About Indoximod
Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target involved in regulating the tumor microenvironment and immune escape. Indoximod is being evaluated in combination with treatment regimens including chemotherapy, radiation, checkpoint blockade and cancer vaccines across multiple indications such as AML, DIPG and melanoma.

On June 4, 2018 Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported it is presenting data on the safety, pharmacodynamics, and clinical activity from the dose escalation stage of the ongoing Phase Ia/b trial of RGX-104, an oral small molecule immunotherapy that targets the liver X receptor (LXR) (Press release, Rgenix, JUN 4, 2018, View Source [SID1234527164]).

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In a poster presentation of an abstract accepted for the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), "Pharmacodynamic and clinical activity of RGX-104, a first-in-class immunotherapy targeting the liver-X nuclear hormone receptor (LXR), in patients with refractory malignancies", Rgenix showed the first-in-class compound to be capable of generating immunologic and anti-tumor activity.

RGX-104 is a small-molecule LXR agonist that modulates innate immunity by activating the ApoE gene. In murine models, the small molecule depletes myeloid derived suppressor cells (MDSCs) and stimulates dendritic cells (DCs), activating anti-tumor immunity as a single agent as well as in combination with adoptive T cell therapy or checkpoint inhibitors. The Phase 1a/b trial in progress is studying the therapy with regards to safety, efficacy, pharmacokinetics and pharmacodynamics. A total of 26 patients with a broad array of tumors have received RGX-104 at a range of dose levels and frequency as part of the dose escalation stage of the study.

RGX-104 was well tolerated across dose cohorts, with hyperlipidemia – an on target effect of LXR agonism – representing the most common adverse event. Robust ApoE target gene engagement was observed in patients, along with substantial MDSC depletion and DC stimulation in 12 of 17 evaluable patients. Activation of circulating PD-1+ T cells was observed in 11 of the 12 patients that experienced MDSC depletion.

One patient with a high-grade neuroendocrine malignancy with small cell features had a confirmed radiographic partial response with a 53% reduction in index hepatic metastases at the 160 mg BID dose. This response was associated with a greater than 12-fold increase in activated PD-1+ T cells. Additionally, seven patients had stable disease for durations of 8-16 weeks. The dose of 160 mg BID was chosen as the Recommended Phase 2 Dose, with robust pharmacodynamic effects on ApoE expression and relevant immune cell populations.

Masoud Tavazoie, MD, PhD, and Chief Executive Officer of Rgenix, said, "Today’s presentation illustrates the promise of our lead clinical candidate RGX-104. It enables us to move forward with our plans to study the compound in expansion cohorts as a single agent as well as in combination with a PD-1 inhibitor in patients with both checkpoint-inhibitor refractory and naïve tumors." Escalation and Expansion cohorts in the Phase 1b stage of the clinical trial are currently enrolling patients with epithelial ovarian carcinoma (EOC), melanoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), renal cell cancer (RCC), bladder cancer (BLC), and triple negative breast cancer (TNBC).