On January 7, 2019 Castle Biosciences, Inc., a skin cancer diagnostics company providing molecular diagnostics to improve cancer management decisions, reported a new publication demonstrating that the DecisionDx-Melanoma gene expression profile (GEP) test can identify high-risk patients who are likely to recur or die from melanoma within groups of patients often considered low risk based on traditional staging metrics (Press release, Castle Biosciences, JAN 7, 2019, View Source [SID1234532533]). Results from this multicenter study of 690 patients demonstrated that the DecisionDx-Melanoma test is an independent predictor of risk for recurrence, metastasis and melanoma-specific death. The study was published in the January 2019 issue of the Journal of the American Academy of Dermatology (JAAD).

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"In this study of a large, contemporary melanoma population, the GEP test identified patients at high risk for recurrence and death from melanoma among groups that are deemed low risk by traditional staging metrics," commented study co-author John Vetto, M.D., Professor of Surgery, Division of Surgical Oncology and Director of the Cutaneous Oncology Program at the Department of Surgery, Oregon Health & Science University. "The 31-gene GEP test provides independent information that improves risk prediction and enables physicians to develop tailored care for their patients with melanoma."

Study Details:

Patients from three previously published DecisionDx-Melanoma validation studies were combined to enable analysis of test performance in the following three clinically important subgroups that are traditionally considered low risk based on current national melanoma guidelines: (1) patients who had a negative sentinel lymph node (SLN) biopsy; (2) those with American Joint Committee on Cancer (AJCC) Stage I-IIA melanoma; and (3) those with thin (≤1 mm) tumors.

The DecisionDx-Melanoma test was performed to determine molecular class for each patient, with a Class 1A result indicating the lowest 5-year risk of metastasis and a Class 2B result indicating the highest risk. Study endpoints included recurrence-free survival (RFS; time to local, regional or distant recurrence), distant metastasis-free survival (DMFS; time to any distant metastasis) and melanoma-specific survival (MSS; time to documented death from melanoma).

In this population of 690 unique Stage I-III patients with at least 5 years of follow-up or a metastatic event, median age was 59 years and median Breslow thickness was 1.3 mm. Seventy percent of patients had Stage I or II melanoma.

Key Study Findings:

In the pooled cohort, patients with Class 1A results had significantly higher RFS, DMFS and MSS rates compared to Class 2B (p<0.0001 for all comparisons).
Seventy percent of the patients who were SLN negative and experienced metastasis were identified as Class 2 by the DecisionDx-Melanoma test. Similarly, 79% of melanoma-specific deaths among those who were SLN negative were identified as having a Class 2 result.
Patients with Stage I-IIA melanoma who received a Class 2B DecisionDx-Melanoma test result had significantly worse RFS, DMFS and MSS rates compared to patients with a Class 1A DecisionDx-Melanoma result (p<0.0001 for all comparisons).
Based on Cox multivariate analysis in the Stage I-IIA subgroup that included tumor thickness, ulceration and mitotic rate, DecisionDx-Melanoma test class was found to be the only significant predictor of all three endpoints (RFS, DMFS and MSS; p<0.05 for all).
For patients with thin tumors (≤1 mm), although most patients were low risk Class 1, 15 patients had the highest risk Class 2B result. Those patients with a Class 2B test result had a significantly reduced RFS of 64.6% compared to those with a Class 1A result (96.8%; p<0.0001).
Results of the study extend previous findings of high prognostic accuracy of the DecisionDx-Melanoma GEP test to subgroups of patients at high risk, yet for whom current national melanoma guidelines recommend low intensity follow-up and surveillance. Additionally, the study’s authors suggest that the results could have an important impact on clinical trials evaluating adjuvant treatment of Stage II disease with immunomodulatory or targeted therapies, as the identification of high-risk Stage II patients may guide appropriate patient enrollment in such trials.

The manuscript can be accessed at View Source(18)32328-4/fulltext

About DecisionDx-Melanoma

The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors and has been studied in over 2,900 patients. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including over 700 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included over 1,400 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in multi-center and single-center studies. More information about the test and disease can be found at www.SkinMelanoma.com.

On January 7, 2019 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that it will be present at the following investor events in the first quarter 2019 (Press release, Innate Pharma, JAN 7, 2019, View Source [SID1234532549]):

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– LifeSci Advisors 1×1 Meetings surrounding the J.P. Morgan Annual Healthcare Conference– San Francisco, January 7-10, 2019

– Oddo BHF Forum – Lyon, January 10-11, 2019

– Degroof Petercam’s Healthcare Seminar – Brussels, January 31, 2019

– Leerink Partners Annual Global Healthcare Conference – NYC, February 27 – March 1, 2019

– Credit Suisse Global Healthcare Conference – London, March 5-6, 2019

– Oppenheimer Annual Healthcare Conference – NYC, March 19-20, 2019

Innate Pharma is committed to meet on a regular basis with the financial community. All corporate information on the Company, such as its financial statements or its corporate presentations, is available on the Company’s websitein the Investors’ section (www.innate-pharma.com/en/investors).

On January 07, 2019 CytoReason, a leader in machine learning for drug discovery and development, reported that it has entered into a collaboration agreement with Pfizer Inc. that will leverage CytoReason’s cell-centered models of the immune system (Press release, CytoReason, JAN 7, 2019, View Source [SID1234619714]).

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CytoReason will receive from Pfizer payments potentially equaling up to low double digit millions of US$ for technology access fees, research support and certain success-based payments.

CytoReason’s proprietary platform helps rebuild lost cellular information from gene expression data and associates genes to specific cells. This information is then integrated with additional omics and literature data to create a cell-based model of the trial-specific immune response. Integration with the CytoReason disease model empowers the study analytics and allows the model to learn and improve, leading to robust target discovery, drug response biomarkers and indication selection.

"We believe that CytoReason’s platform has the potential to offer valuable insights that may be applied to our research into the human immune system," said Michael Vincent, Chief Scientific Officer, Inflammation & Immunology, Pfizer. "Leveraging technologies such as this can help us understand disease and prioritize targets, and support our mission of bringing innovative new therapies to patients who need them."

"The collaboration with Pfizer will further strengthen our models in our core therapeutic areas. This will be our fifth major partnership, which we believe will help make our model unparalleled in its accuracy for assets across the pipeline," said David Harel, CytoReason’s CEO. "CytoReason’s model brings together thousands of samples on a cell-protein-gene level, allowing for fast and accurate insights."

About CytoReason

Based on more than 10 years of research, CytoReason’s technology uses a proprietary data and machine learning model to reconstruct cellular information from bulk tissue, to train an immune-specific NLP engine, and to integrate multi-omics data. The company’s platform organizes and standardizes collaborators’ data (gene, protein, cell, and microbiome) and integrates it into CytoReason’s proprietary disease model to generate mechanistic understanding of the immune system, leading to novel insights.

CytoReason’s technology has yielded 2 pending patents, 10 commercial and scientific collaborations and 16 peer reviewed publications. Fully applicable to cancer immunotherapy, autoimmune, neurodegenerative and infectious disease research, CytoReason is at the cutting edge of society’s boldest attempts to improve health outcomes through better understanding of the immune system.

On January 7, 2019 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported anticipated 2019 milestones for IPI-549, a first-in-class, oral, immuno-oncology product candidate targeting tumor-associated myeloid cells through selective phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibition and provided financial guidance for 2019 (Press release, Infinity Pharmaceuticals, JAN 7, 2019, View Source [SID1234532501]).

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"In the year ahead, we are excited to be moving into earlier lines of therapy, new indications, and novel, potentially transformative immuno-oncology combinations to execute on our strategy to expand the depth and breadth of the development of IPI-549," said Adelene Perkins, Chief Executive Officer of Infinity Pharmaceuticals. "Importantly, we have a cash runway into the second half of 2020, which enables us to advance IPI-549 development in several innovative studies in 2019. We also have the support of tremendous collaborators BMS and Arcus for two of these potentially transformative studies."

"The IPI-549 safety and clinical activity from the MARIO-1 Phase 1b study continues to inform our strategy to expand the depth and breadth of IPI-549 development for cancer patients," said Dr. Sam Agresta, Chief Medical Officer of Infinity. "MARIO-275 is our first global, randomized study of IPI-549 in combination with Opdivo compared to Opdivo monotherapy. This study, in collaboration with BMS, is designed to address an unmet medical need for patients with advanced urothelial cancer and is an important step in advancing IPI-549 development beyond the checkpoint inhibitor refractory setting. In addition, the safety, clinical activity and mechanism of action of IPI-549 allows us to expand the breadth of the program by moving into novel combinations, including in previously treated, advanced triple negative breast cancer patients, with a novel triple therapy study in collaboration with Arcus. And I am particularly excited to initiate our first IPI-549 study in the front-line setting in 2019."

Infinity plans to initiate MARIO-275, a combination study of IPI-549 with Opdivo in I/O naïve urothelial cancer (UC) patients, in the first half of 2019. Opdivo was approved for use by the FDA as a single agent in advanced urothelial cancer based on durable response associated with treatment in CheckMate-275, a Phase 2 single arm clinical trial of Opdivo in subjects with metastatic or unresectable urothelial cancer who have progressed or recurred following treatment with a platinum agent1. Retrospective analyses of this study showed that patients with higher levels of myeloid derived suppressor cells, or MDSCs, had poor outcomes2. IPI-549 has been shown to reduce MDSCs as both a monotherapy and in combination with Opdivo in MARIO-13-6. MARIO-275 is intended to evaluate the benefit of adding IPI-549 to Opdivo in cisplatin-refractory, I/O-naive urothelial cancer patients. Clinical benefit will be assessed in the overall population as well as in subsets of patients with different baseline levels of MDSCs.

Infinity will also be advancing novel triple combination therapies with Arcus, initially evaluating IPI-549 in combination with AB928, Arcus’s dual adenosine receptor antagonist, and chemotherapy in patients with previously treated, advanced triple negative breast cancer, or TNBC. As both macrophages and high adenosine levels are believed to play critical roles in creating a highly immune-suppressive tumor microenvironment in cancer after chemotherapy, the novel immuno-oncology combination being evaluated in this setting represent a potentially promising approach to treating TNBC.

Infinity’s chair and chief executive officer, Adelene Perkins, will discuss the company’s continued execution on its corporate strategy and 2019 priorities as part of a podium presentation at the 37th Annual J.P. Morgan Healthcare Conference on Thursday, January 10, at 9:30 a.m. PST (12:30 p.m. EST). The presentation will be webcast live on Infinity’s website, www.infi.com, and an archived version of the webcast will be available on Infinity’s website for 30 days.

Anticipated Milestones in 2019: Expanding Depth and Breadth of IPI-549 Development

1H2019

Advance into Immuno-Oncology (I/O) Naïve Indications in Combination with Opdivo: Initiate MARIO-275 in I/O naïve UC patients with BMS
Advance into Novel Triple Combinations Beyond CPIs: Initiate Triple Therapy Combination (IPI-549+AB928+Chemo) in previously treated advanced TNBC with Arcus
2H2019

Initiate the first IPI-549 combination study in front-line advanced cancer patients
Complete enrollment of MARIO-1 seven combination expansion cohorts including:
Augmented melanoma expansion cohort (n=40)
TNBC expansion cohort (n=29)
2019 Financial Guidance

Infinity ended 2018 with approximately $58.6 million in cash and investments (unaudited) and plans to report its fourth quarter and full-year 2018 financial results in March. The company is providing the following financial guidance today:

Net loss: $30 million to $40 million
Year-end cash: $20 million to $30 million
Cash runway: Into 2H 2020
Infinity’s 2019 financial guidance is based on its current operating plans, excludes additional financing or business development activities, and includes a $2 million milestone payment from PellePharm, a private company, upon initiation of a Phase 3 study for the hedgehog inhibitor program, which Infinity licensed to PellePharm in 2013.

IPI-549 is an investigational compound, and its safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On January 7, 2019 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported a 2019 clinical and corporate outlook (Press release, Syndax, JAN 7, 2019, View Source [SID1234532534]).

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"2019 is slated to be a milestone-rich time for Syndax, with data expected from multiple trials within our ENCORE program of entinostat in combination with checkpoint therapy in platinum resistant ovarian cancer, triple negative breast cancer, and anti-PD-1-pretreated melanoma, all of which we believe represent underserved areas with significant market opportunity," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "We also eagerly anticipate the next interim overall survival analysis in the second quarter from the Phase 3 E2112 trial of entinostat plus exemestane in HR+, HER2- breast cancer and remain highly encouraged by the potential to provide a survival benefit for HR+, HER2- breast cancer patients who have stopped responding to first line treatment with hormone therapy. Any positive overall survival assessment would enable the company to file for full regulatory approval."

Dr. Morrison added, "In addition, we remain on track for an IND filing for our Menin inhibitor, SNDX-5613, in the second quarter of 2019, followed by initiation of the clinical trial program. Acute leukemias characterized by MLL-rearrangements and nucleophosmin mutations represent areas of high unmet medical need, and the preclinical data we’ve generated thus far provide strong support that menin inhibition has the potential to serve as an effective therapy for patients lacking viable options. Finally, we continue to expect initial efficacy results for SNDX-6352 in chronic graft versus host disease in the second half of 2019."

Anticipated Key Milestones for 2019:

Entinostat

Topline results from the randomized Phase 2 portion of the ENCORE 603 trial of entinostat in combination with Pfizer/Merck KGaA’s PD-L1 inhibitor, BAVENCIO (avelumab), in patients with ovarian cancer are expected in the first quarter of 2019.
Presentation of clinical, biomarker and gene analysis data from the anti-PD-1 pretreated melanoma cohort of the Phase 2 ENCORE 601 trial of entinostat in combination with KEYTRUDA (pembrolizumab) is expected in the first quarter of 2019.
A decision on whether to advance to the second stage of the ENCORE 601 cohort of patients with microsatellite stable colorectal cancer (MSS-CRC) naïve to PD-1 therapy is expected in the first quarter of 2019.
Topline results from the randomized Phase 2 portion of the ENCORE 602 trial of entinostat in combination with Genentech’s PD-L1 inhibitor, TECENTRIQ (atezolizumab), in patients with triple negative breast cancer are expected in the second quarter of 2019.
The next interim analysis for the overall survival (OS) primary endpoint of E2112, the Phase 3 registration trial of entinostat plus exemestane in advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer, is expected in the second quarter of 2019. Additional interim analyses will be conducted every six months until either an OS benefit is observed, or the final target number of events occur. Any positive OS assessment would enable the Company to file for full regulatory approval.
Syndax plans to commence a focused, biomarker-driven, randomized registration trial comparing the entinostat-pembrolizumab combination to standard of care chemotherapy in non-small cell lung cancer (NSCLC) patients whose disease has progressed after both platinum-based chemotherapy and PD-1 antagonist therapy in the first half of 2019. The trial will seek to validate peripheral classical monocytes as a marker of response to the combination and to determine whether the combination can improve progression free survival (PFS) over standard of care chemotherapy in the high monocyte population.
SNDX-6352

Topline results and a recommended Phase 2 dose and schedule from the Phase 1/1b trial of SNDX-6352, Syndax’s anti-CSF-1R monoclonal antibody, alone or in combination with IMFINZI (durvalumab), AstraZeneca’s human monoclonal antibody directed against PD-L1, are expected in the second quarter of 2019.
Topline results and a recommended Phase 2 dose and schedule from the Phase 1 trial of SNDX-6352 in patients with chronic graft versus host disease (cGVHD) are expected in the third quarter of 2019.
Menin-MLLr Inhibitor Portfolio

An Investigational New Drug (IND) filing with the FDA for SNDX-5613, the Company’s lead Menin inhibitor compound, is expected in the second quarter of 2019, followed by the initiation of a Phase 1 clinical trial in patients with a genetically defined subset of acute leukemias.
Financial Guidance

Syndax ended 2018 with cash, cash equivalents and short-term investments of approximately $80 million. For 2019, research and development expenses are expected to be $54 to $58 million, and total operating expenses are expected to be $68 to $73 million. Research and development expenses and total operating expenses for 2019 are expected to include approximately $2 million and $6 million, respectively, of non-cash stock compensation. The Company plans to announce financial results from the fourth quarter and full-year 2018 later this quarter.