On April 18, 2018 Genocea Biosciences, Inc. (NASDAQ:GNCA), a biopharmaceutical company developing neoantigen cancer vaccines, reported highlights from its scientific presentations at the 2018 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2018), taking place April 14-18, 2018 in Chicago, IL (Press release, Genocea Biosciences, APR 18, 2018, View Source [SID1234525509]).

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Jessica Flechtner, Ph.D., Genocea’s chief scientific officer commented on the AACR (Free AACR Whitepaper) presentations: "We continue to generate data that demonstrate the versatility of our ATLAS platform. As the studies presented at AACR (Free AACR Whitepaper) indicate, ATLAS is a differentiator for Genocea – allowing us to do what in silico approaches cannot – to both identify and characterize neoantigens for use in personalized cancer vaccines. We believe that our ability to find stimulatory and inhibitory antigens during the neoantigen selection process combined with our capacity to explore mechanisms of inhibitory antigens in a murine model, may enable us to help cure cancer by pioneering next-generation cancer vaccines."

Summary of AACR (Free AACR Whitepaper) Poster #730, "Empirical neoantigen identification using the ATLAS platform across thousands of mutations and multiple tumor types highlights advantages over algorithmic prediction methods":

ATLAS enables identification of biologically relevant CD4+ and CD8+ T cell neoantigens in subjects in an unbiased manner, by using subjects’ own antigen-presenting cells (APCs) and T cells rather than predictive algorithms to identify and characterize T cell responses to all candidate neoantigens.
Neoantigen screening was performed on 23 individuals across eight tumor types with mutational burden ranging from 9 to 319 unique mutations.
Empiric identification of neoantigens derived from somatic mutations from each patient’s tumor independently of HLA type and without predictions resulted in the following observations:
ATLAS identified stimulatory neoantigens of both CD4+ and CD8+ T cells, which Genocea believes confirms the importance of including antigens of relevance for both T cell subsets in neoantigen vaccines;
There is little overlap between CD4+ and CD8+ T cell neoantigens; fewer than 2% of empirically confirmed neoantigens were shared between T cell subsets;
Prediction algorithms missed up to 69% of ATLAS-identified neoantigens, with only 2% of CD8+ neoantigens and 24% of CD4+ neoantigens accurately predicted;
The major histocompatibility complex (MHC) class I algorithm appeared to better predict CD4+, not CD8+, neoantigens;
ATLAS also identified inhibitory neoantigens of both CD4+ and CD8+ T cells
Inhibitory neoantigens outnumbered stimulatory neoantigens more than three-fold in aggregate in the screened patients;
Inhibitory antigens currently cannot be identified using in silico approaches.
Summary of Poster #5718, "ex vivo ATLASTM identification of neoantigens for personalized cancer immunotherapy in mouse melanoma":

The B16F10 mouse melanoma model was utilized to characterize neoantigens. More than 1,600 tumor-specific mutations (possible neoantigens) were interrogated using the ATLAS technology and CD8+ T cells from tumor-bearing C57BL/6 mice.
Similar to human neoantigen screens, mouse ATLAS (mATLAS) identified both stimulatory and inhibitory neoantigens:
99% of mutations identified using whole exome sequencing were screened;
68 stimulatory (4% of total mutations) and 57 inhibitory (3% of total mutations) neoantigens were identified.
NetMHCPan, a MHC-binding prediction algorithm, failed to identify the majority of mATLAS-identified neoantigens:
Only 2% of B16F10 neoantigens predicted by algorithms were empirically confirmed to be stimulatory antigens;
91% of stimulatory neoantigens empirically identified with mATLAS were not predicted;
6% of algorithm-predicted neoantigens were inhibitory.
These data demonstrate that inhibitory antigens can be identified in mouse models, allowing for future research into the mechanism of ATLAS-identified inhibitory responses and their relationship to stimulatory neoantigens in mediating tumor control.

On April 18, 2018 OBI Pharma, Inc., a Taiwan biopharma company (TPEx: 4174), reported that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for a Phase I/II study of OBI-3424, a first-in-class DNA alkylating agent that targets cancers that overexpress the aldo-keto reductase 1C3 (AKR1C3) enzyme (Press release, OBI Pharma, APR 18, 2018, View Source [SID1234525525]).

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OBI plans to enroll patients with local solid tumors, including hepatocellular carcinoma (HCC) and castrate-resistant prostate cancer (CRPC). OBI Pharma’s Chief Medical Advisor, Tillman Pearce, M.D., noted, "This clinical trial intends to verify the safety and preliminary activity profile of OBI-3424, a novel first-in-class prodrug of a DNA alkylating cancer therapeutic that is selectively activated by AKR1C3, an enzyme that is overexpressed in a variety of solid and liquid tumors. We are delighted to conduct this first-in-man clinical trial at the University of Texas M.D. Anderson Cancer Center and The James Cancer Hospital and Solove Research Institute of Ohio State University, two of America’s leading academic oncology research institutions".

Amy Huang, General Manager of OBI Pharma, added, "OBI Pharma is proud to further develop our unique targeted cancer pipeline, including targets like the Globo series and AKR1C3. OBI-3424 enhances OBI’s pipeline in solid and liquid tumors for cancer patients who over-express AKR1C3. OBI is taking a first-step towards testing the safety and initial efficacy of a new class of AKR1C3 targeted therapy. We are excited to develop novel targeted therapeutics in the fight against cancers of unmet need."

About OBI-3424

OBI-3424 is a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1C3 (AKR1C3), and selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.

AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult-to-treat cancers including: hepatocellular carcinomas (HCC), castrate-resistant prostate cancer (CRPC), and T-cell acute lymphoblastic leukemia (T-ALL). AKR1C3 is highly expressed in up to 15 solid and liquid tumors.

Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed based on tumor biopsies or circulating tumor cells to identify patients with other tumor types most likely to respond to treatment with OBI-3424, and thus offering the possibility for a streamlined clinical development strategy.

OBI Pharma holds worldwide rights for OBI-3424 with the exception of the following countries, whose rights are held by Ascenta Pharma: China, Hong Kong, Macao, Taiwan, Japan, South Korea, Singapore, Malaysia, Thailand, Turkey, and India.

On April 18, 2018 Computational drug design company Numerate reported that it has signed a letter of intent to join an open consortium of scientists staffed from two U.S. national laboratories, industry, and academia working to transform drug discovery and development into an approach that is rapid, integrated and with better patient outcomes (Press release, Numerate, APR 18, 2018, View Source [SID1234525510]).

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Accelerating Therapeutics for Opportunities in Medicine (ATOM) formed in October 2017 with the goal of reducing preclinical drug discovery from six years to just one, using cancer as the exemplar disease.

ATOM is integrating high-performance computing and biological, chemical, preclinical, and clinical data from public and industry sources to create an active learning platform that considers all aspects of drug discovery and pharmacology. ATOM will integrate emerging high-fidelity, data-rich experimental technologies, and cutting-edge software into the approach.

"This will create an ecosystem which will foster the rapid and dynamic collaboration needed to advance precision medicine and tremendously benefit patients," wrote Guido Lanza, president and CEO of Numerate, and Brandon Allgood, CTO, in the letter signed April 3, 2018.

"Our organization’s business priorities and directions are strongly aligned with the fundamental elements of ATOM … and we look forward to outlining the specific contributions we can make to the ATOM consortium as collaborators," they wrote.

John Baldoni, ATOM founder and governing board co-chair, and senior vice president for R&D at GSK, said Numerate is well-known for its innovative software approach to drug discovery.

"This collaboration provides Numerate with extensive and unique data sources and computer power with which they can optimize their drug discovery algorithms," Baldoni said. "This letter of intent signals how cutting-edge private-sector organizations can benefit in this public/private consortium."

Numerate joins the founding members of ATOM: GSK, the National Cancer Institute’s Frederick National Laboratory for Cancer Research (FNLCR), the University of California, San Francisco (UCSF), and the Department of Energy/National Nuclear Security Administration (NNSA)’s Lawrence Livermore National Laboratory (LLNL), which is contributing supercomputer resources and cognitive simulation expertise to the ATOM consortium. ATOM headquarters is located in the Mission Bay neighborhood of San Francisco.

ATOM seeks other organizations to join the consortium to bring their expertise into this new environment.

"We are excited to see the addition of industry leaders to the consortium and to the effort to bring effective new drugs to cancer patients more rapidly," said Eric Stahlberg, director of high performance computing at the Frederick National Laboratory.

The partners agree to work together to develop, test, and validate a multidisciplinary approach to drug discovery where science, technology and engineering, supercomputing simulations, data science, and artificial intelligence are integrated into a drug-discovery platform, ultimately to be shared with the drug development community at large.

On April 17, 2018 ArQule, Inc. (NASDAQ:ARQL) reported that it has entered into an exclusive license agreement with Basilea Pharmaceutica International Limited(Basilea, SIX: BSLN) to develop and commercialize derazantinib, a pan-FGFR (fibroblast growth factor receptor) inhibitor in the US, EU, Japan and rest of the world excluding the People’s Republic of China, Hong Kong, Macau and Taiwan, where Sinovant Sciences Ltd., a Roivant Sciences Ltd. subsidiary, has rights to develop and exclusively commercialize the drug (Press release, ArQule, APR 17, 2018, View Source [SID1234525419]).

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Under the terms of the agreement, ArQule will receive an upfront payment of $10 million and is eligible for up to $326 million in regulatory and commercial milestones. ArQule is also entitled to receive staggered single-digit to double-digit royalties on net sales upon commercialization. Basilea will be responsible for all costs and expenses of development, manufacture and commercialization in its territory. Under certain circumstances, ArQule may have the opportunity to promote derazantinib in the US directly.
ArQule is currently conducting a registrational trial for derazantinib in the United States, Canada and Europe as a potential treatment for intrahepatic cholangiocarcinoma (iCCA), a form of biliary tract cancer. As part of the exclusive license agreement, Basilea intends to continue this trial and the further development of derazantinib in iCCA and other tumor types with FGFR dysregulation.

Ronald Scott, Chief Executive Officer of Basilea, said: "We are very excited about this partnership with ArQule. Derazantinib is an ideal match for our existing clinical oncology portfolio. It is a targeted therapy building on a solid biomarker approach in an area where patients currently have limited treatment options. This transaction underscores our continued commitment to expand our R&D portfolio with novel compounds focused on overcoming the clinical problem of resistance in oncology and infectious diseases. Our clinical oncology portfolio now includes three drug candidates in different stages of development. We continue to focus on further broadening our R&D portfolio through internal and external innovation."

"Partnering with Basilea, a company with global drug development experience and expertise, will propel the advancement of derazantinib in ways we could not have achieved independently," said Paolo Pucci, Chief Executive Officer of ArQule. "Basilea will bring a wealth of skills to the expansion of the derazantinib development plan at a time when it will benefit most from these resources, allowing it to reach its full potential in iCCA and beyond."
ArQule will hold a conference call to discuss this agreement tomorrow, April 18, beginning at 9 a.m. EDT. Paolo Pucci, Chief Executive Officer of ArQule, will lead the call. As a result of entering into the exclusive license agreement, ArQule will be updating its financial guidance on the call.

The details of the call are as follows:
Wednesday, April 18, 2018 at 9:00 AM EDT
Audio connection numbers:
US: 1 877-868-1831
Outside US: 1 914-495-8595 PIN: 4089669
A replay of the call will be available two hours after the completion of the call and can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations." The ArQule investor conference call will be archived and can be accessed in the "Investors and Media" section of ArQule’s website, www.arqule.com, under "Events and Presentations."
About Derazantinib
Derazantinib is a potent, orally administered inhibitor of the fibroblast growth factor receptor (FGFR) family, a key driver of cell proliferation, differentiation, and migration. In a Phase 1/2 study in patients with iCCA harboring FGFR2 gene fusions, treatment with derazantinib resulted in an objective response rate of 21%, nearly 3 times higher than standard-of-care chemotherapy. ArQule is currently conducting a registrational study with derazantinib in patients with FGFR2 fusion-positive second-line iCCA. The open-label single-arm trial is recruiting in the United States, Canada and Europe with objective response rate as the primary endpoint. More information on that program is available here.
About Intrahepatic Cholangiocarcinoma
Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC).1 Depending on the anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA), and extrahepatic (eCCA). iCCA originates from the intrahepatic biliary ductal system and forms an intrahepatic mass. iCCA is an aggressive cancer, with a median 5-year survival rate of 15% for patients diagnosed with early-stage disease.2 In China, the incidence of cholangiocarcinoma is more than 7 cases per 100,000 people, and the majority of cases are intrahepatic.3

On April 17, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported that worldwide net sales of DARZALEX (daratumumab) as reported by Johnson & Johnson were USD 432 million in the first quarter of 2018 (Press release, Genmab, APR 17, 2018, View Source [SID1234525439]). Net sales were USD 264 million in the U.S. and USD 168 million in the rest of the world. Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

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About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL and selected solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.. Net sales were USD 264 million in the U.S. and USD 168 million in the rest of the world. Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL and selected solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.