On December 17, 2020 Glycotope GmbH, an oncology/immuno-oncology platform company built on world-leading glycobiology expertise, reported that is has signed an agreement to license a humanized, tumor-specific antibody (GlycoBody) targeting an aberrantly glycosylated tumor associated form of MUC1 (TA-MUC1) to ONK Therapeutics Ltd. (ONK), an innovative natural killer (NK) cell therapy company (Press release, Glycotope, DEC 17, 2020, View Source [SID1234572966]).

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The GlycoBody will be integrated into ONKs pre-clinical program ONKT103, for solid tumors. ONK’s unique platform approach combines the expression of a chimeric antigen receptor (CAR) and a high affinity, membrane-bound TNF related apoptosis inducing ligand variant (TRAILv).

Multiple solid tumor types express the mucin MUC1, including non-small cell lung cancer, breast cancer and ovarian cancer. MUC1 is also expressed on healthy tissues and previous attempts to target this antigen have proved problematic. By utilizing Glycotope’s antibody, ONK can tailor its CAR to target the glycosylation pattern distinct to tumor associated MUC1 (TA-MUC1) with specific recognition of the carbohydrate antigens Tn and T on MUC1. The expression of these antigens is restricted to cancer cells and by targeting them ONK hopes to increase tumor-specificity and reduce the potential for on-target off-tumor toxicity.

Henner Kollenberg, Managing Director of Glycotope GmbH commented "This is an exciting development. Our technology platform has identified the glycosylation pattern that could enable ONK to unlock the potential of TA-MUC1 as a solid tumor target with their unique dual-targeted NK cell therapy approach. This represents further validation of our platform’s ability to enable the development of highly-specific immunotherapies across a broad range of cancer indications."

On December 17, 2020 Lantern Pharma (Nasdaq: LTRN), a clinical-stage biopharma company using its proprietary RADR artificial intelligence ("A.I.") platform to transform cancer drug development and identify patients who will benefit from its targeted oncology therapeutics, reported a collaboration and research agreement with the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Kennedy Krieger Institute (Press release, Lantern Pharma, DEC 17, 2020, View Source [SID1234572987]). The collaboration will focus on the further development of Lantern’s LP-184 in glioblastoma multiforme (GBM). Based in Baltimore, Johns Hopkins is a leading research center for brain cancers and one of the largest brain tumor treatment and research centers in the world with a focus on treating an extremely large number of patients affected by all types of brain tumors.

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The collaboration will focus on advancing the targeted use of LP-184 in defined subtypes of GBM and clarifying the most promising clinical applications for the drug candidate. The goal of the collaboration is to develop a clinically ready program that has characterized the drug candidate with the most biologically relevant and robust genomic or biomarker signature. By having a gene signature that can be used in identifying patients that have the potential for the highest response, Lantern can potentially accelerate future clinical trials and shorten the time to achieving patient benefit for GBM patients.

The research program is at the forefront of translational cancer medicine and will use patient-derived cancer cells that are studied using physiologically relevant in vitro and in vivo models. This innovative approach allows researchers to more precisely understand the biology of what actually happens inside the cancer tumor, which will more accurately establish the precise biomarker signatures and help provide data-driven insight into additional mechanisms that can be leveraged in the fight against brain cancer.

"Collaborations with world-leading cancer centers are an essential part of our strategy to rapidly advance the insights driving our therapeutic programs and grow the power of our RADR A.I. platform by adding millions of new, unique, and proprietary data points in areas of high unmet need in cancer," said Panna Sharma, CEO of Lantern Pharma. "This relationship with Johns Hopkins is expected to allow us to use state-of-the-art models and biological methods to add more physiologically relevant data and insights into the mechanisms of LP-184, and further shape our algorithms for how our drug candidates interact with specific brain cancer subtypes. We believe the unique insights we gain will equip Lantern with critical advantages in our aim of accelerating LP-184’s path to clinical trials and ultimately commercialization while saving millions of dollars in development costs. This data-enabled and biomarker-based approach has the potential to meaningfully bend the cost curve of cancer drug development and help bring personalized cancer therapies to patients with reduced economic burden, and greater efficacy."

The research will be led by John Laterra, MD, Ph.D., an internationally recognized researcher in neurology, oncology, and neuroscience. Dr. Laterra serves as the Co-Director of the Brain Cancer Program and the Director of the Division of Neuro-Oncology at Johns Hopkins School of Medicine where he specializes in investigating mechanisms of brain tumor malignancy, tumor vascular biology, and identification of new therapeutic targets in gliomas.

LP-184 is a DNA-damaging small molecule drug candidate currently in preclinical development for certain genomically defined solid tumors, including glioblastomas. As a next-generation alkylating agent that preferentially damages DNA in cancer cells that overexpress certain biomarkers and can cross the blood-brain barrier, we believe LP-184 has the potential to be used as both monotherapy as well as a synergistic agent in combination with other drugs.

"We are focused on finding how LP-184 can exploit certain molecular mechanisms in gliomas to offer improved disease management and survival for glioblastoma patients," said Dr. Kishor Bhatia, Chief Scientific Officer at Lantern Pharma. Dr. Bhatia continued, "We look forward to our collaboration with Johns Hopkins, the Brain Cancer Program and Dr. Laterra who is at the forefront of GBM research. His approach combines real world patient insights along with advanced methodologies and patient-derived models that can improve the quality of the insight and provide more relevant data on efficacy. We look forward to sharing these results with the broader scientific and clinical community."

Among several objectives, the research goals are to determine whether certain genomic signatures generated with RADR, Lantern’s A.I. platform, can predict response to LP-184 and a more favorable outcome as compared to standard of care agents being used today. LP-184 has been advanced using Lantern’s proprietary RADR A.I. platform that leverages over one billion curated cancer data points, machine learning, genomics, and computational biology to accelerate the discovery of potential mechanisms of action, and biomarker signatures that correlate to drug response in cancer patients.

Although significant recent advances have been made in the use of targeted and biomarker-based therapies in cancer, GBM remains an area that has not experienced significant improvement in patient outcomes. The overall five-year survival rate for GBM across all stages remains at only 5.5% in the US, and GBM accounts for nearly 52% of all primary brain tumors each year according to the National Cancer Institute.

On December 17, 2020 Stand Up To Cancer (SU2C) reported that unveiled a collaborative initiative aimed at improving colorectal cancer screening, early detection and prevention across the United States (Press release, Exact Sciences, DEC 17, 2020, View Source [SID1234573009]). The transformative $10 million grant from Exact Sciences, a provider of cancer screening and diagnostic tests, will fund a colorectal cancer ‘Dream Team’ of researchers, as well as a comprehensive public awareness campaign to increase screenings.

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The new Dream Team will be awarded in early 2021 and will identify communities near anchor institutions that serve minority and medically underserved communities, pinpoint the unique local needs of those areas and turn participating at-risk communities into "Stand Up To Cancer Zones" with high rates of colorectal cancer screening. The Dream Team will provide free colorectal cancer testing in the identified zones and will study samples collected via approved tests for colorectal cancer, including colonoscopy, CT colonography, flexible sigmoidoscopy, and at-home stool tests that analyze fecal DNA and/or blood. The research will aim to develop better approaches to colorectal cancer interception.

Fellowships for early-career investigators committed to studying health equity and disparities in colorectal cancer will also be funded. Public awareness campaigns will focus on medically underserved communities to increase awareness of the importance of colorectal cancer screening and early detection, and the availability of multiple effective screening options, such as traditional colonoscopy as well as options used at home.

"This funding allows us to bring together institutions, clinicians and communities to address the challenges we face in colorectal cancer screening," said Nobel laureate Phillip A. Sharp, PhD, chair of Stand Up To Cancer’s Scientific Advisory Committee and an Institute professor at the David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology. "Due to the COVID-19 pandemic, it’s more important than ever to make sure people are informed about both the benefits of colorectal cancer screening and their options."

"We’re excited to work with Stand Up To Cancer on this bold new initiative," said Kevin Conroy, chairman and CEO of Exact Sciences. "We want to change the way people think about colorectal cancer screening. This collaboration will move cutting-edge research and education efforts forward so we can help more people."

This year, nearly 148,000 Americans will receive a new diagnosis of colon or rectal cancer.i Colorectal cancer is treatable in 90% of cases when detected early,ii yet 1 in 3 adults over age 50 are not up-to-date on recommended colorectal cancer screening.iii The COVID-19 pandemic has further compounded the problem with screening rates dropping significantly due to stay-at-home orders. For example, the total number of colonoscopies and biopsies performed declined by nearly 90% by mid-April 2020 compared to April 2019.iv Concurrently, new cases of colorectal cancer are occurring at a growing rate among young and middle-aged adults in the US, with the number of cases of colorectal cancer in people under 50 expected to almost double by 2030.v The disease disproportionately impacts people of color; Black people have the highest rates of colorectal cancer of any racial or ethnic group in the US.vi In October 2020, the US Preventive Services Task Force released a draft recommendation to lower the colorectal cancer screening age from 50 to 45,vii but educating the public about the benefits of screening, as well as screening options, remains vital.

"We want people to understand that this disease is highly preventable and that a simple test can save lives," said Sung Poblete, PhD, RN, CEO of Stand Up To Cancer. "When it comes to screening for colorectal cancer, the best test is the test that gets done. People will always benefit from simple and accessible healthcare options, and at-home preventive care is particularly vital to keeping people healthy during the pandemic. Together with Exact Sciences, we’re going to make this message mainstream and our hope is that other collaborators, such as healthcare providers, community leaders and advocacy groups, will join us in taking a stand against colorectal cancer."

Research has shown that colorectal cancer screening rates are the lowest in Hispanic communities, with 59% of Hispanics getting screened, compared to 66% of Black people and 69% of white people getting screened.viii Black and Hispanic people are typically diagnosed at a later stage in the disease when it is more difficult to treat. These disparities could be driven by financial barriers, lack of insurance, existing health inequities and insufficient information about colorectal cancer and colorectal cancer screening options.

SU2C, along with Exact Sciences, plans to engage with other collaborators to help reach the underserved communities, foster scientific research and guide public participation. The multi-pronged approach intends to ensure that colorectal cancer remains a disease that is treatable and survivable through widespread screening and early detection.

SU2C announced a Health Equity Initiative in January 2020. The initiative requires all future teams seeking Stand Up To Cancer funding to address recruitment and retention of patients from different ethnic and racial groups and underserved communities to improve diverse participation in cancer clinical trials. The initiative also includes collaborations with advocacy groups and industry and corporate supporters to move research and public awareness efforts forward. The new grant from Exact Sciences is the next critical step in SU2C’s movement to ensure cancer research, screening and treatment benefit everyone.

On December 16, 2020 ONA Therapeutics, Absolute Antibody and RIC-three leading European companies in the biotech landscape reported that have been awarded a Eurostars grant for a two-year project that will develop a proprietary biological drug with a unique mode of action for the treatment of various types of metastatic cancers (Press release, Ona Therapeutics, DEC 16, 2020, View Source [SID1234572930]). Taking the lives of more than 9 million people globally each year, metastatic cancers are often unresponsive to existing cancer treatments, leaving a large unmet need. In order to tackle this important health problem, the newly established consortium-named LIPOLOGIC-will combine industry know-how in complementary areas of drug development: from target discovery, across molecule formatting and manufacturing, to lead selection and characterization.

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ONA Therapeutics, a Spanish biotech company specialized in the discovery and development of therapeutic biologics targeting tumor metastatic-initiating cells and lipid metabolism, will take the lead in the LIPOLOGIC program. "Our research demonstrates that the survival of metastatic cells is linked to the intake of certain saturated fats and if we block the capacity for intake of these fats, we significantly reduce the cell’s metastatic potential. We are excited to partner with Absolute Antibody and RIC to develop novel revolutionary therapies that target this mechanism of action and with the potential to treat multiple types of metastatic cancer" said ONA co-founder and CEO Valerie Vanhooren.

Absolute Antibody, experts in recombinant antibody technology, will engineer the biologic into an optimized format and then recombinantly produce and purify the molecule for preclinical analysis. According to Ian Wilkinson, Chief Scientific Officer, "Our contribution to the team will result in a reproducible, defined biologic to progress to the IND stage and clinical trials. We are very excited about the potential of this unique mode of action."

RIC, expert in biopharma analytics, will apply its comprehensive knowledge and in-house platforms to provide the CMC data necessary for evaluating the project’s candidate molecules and selecting the best lead: identifying physicochemical liabilities, better understanding target binding through epitope mapping and evaluating overall pharmacokinetics. "The complex nature of biological products makes the development of innovative therapies like these truly challenging. We are proud to bring our analytical skill set to the table and help make this new type of treatment a reality" said Koen Sandra, CEO at RIC.

The LIPOLOGIC consortium has just kicked off its pre-clinical development against a variety of tumor types and plans to move its lead candidate into first clinical studies in patients with metastatic cancer in the upcoming years. The initiative is funded by the Eurostars-2 joint programme with co-funding from the European Union Horizon 2020 research and innovation programme.

On December 16, 2020 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a late clinical-stage biopharmaceutical Company focused on oncology, reported results from the triple combination arm of the Company’s COMBAT/KEYNOTE-202 clinical study evaluating motixafortide (BL-8040) in combination with KEYTRUDA (pembrolizumab) and chemotherapy in patients with second-line stage IV pancreatic ductal adenocarcinoma (PDAC) (Press release, BioLineRx, DEC 16, 2020, View Source [SID1234572948]).

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A total of 43 patients initially diagnosed with unresectable stage IV metastatic PDAC, who had progressed following first-line gemcitabine-based therapy, were enrolled in the triple combination arm. Patients received motixafortide monotherapy priming treatment for five days, followed by combination cycles of motixafortide, KEYTRUDA and chemotherapy (Onivyde/5-fluorouracil/leucovorin) until progression. The primary endpoint of the study is the objective response rate (ORR); secondary endpoints include confirmed objective response rate (cORR), overall survival (OS), progression free survival (PFS), and disease control rate (DCR).

The results of the study showed substantial improvement as compared to historical results across all study endpoints. Data are summarized below for the evaluable patients in the study (n=38).

Data summary:

COMBAT/KEYNOTE

HISTORICAL DATA

Median overall survival (mOS)

6.5 months

4.7 months1

Median progression free survival (mPFS)

4.0 months

2.7-3.1 months2,3

Confirmed overall response rate (cORR)

13.2%

7.7%3

Overall response rate (ORR)

21.2%

16%1

Disease control rate (DCR)

63.2%

29-52%2,4

1 Macarulla Mercade et al, Pancreas 2020
2 Petrelli et al Eu J Cancer 2017
3 Onivyde prescribing information
4 Wang Gillam Eu J Cancer 2019

The combination was generally well tolerated, with a safety profile consistent with the individual safety profile of each component alone; adverse event (AE) and severe adverse event (SAE) profiles were as expected with chemotherapy-based treatment regimens. Of note, certain safety advantages were demonstrated by the triple combination of motixafortide, KEYTRUDA and chemotherapy, when compared to historical data relating to the specific chemotherapy used in the study. These safety advantages include incidence of grade 3 neutropenia (7% versus historical data of 20%) and incidence of grade 3 infections (7% versus historical data of 17%).

"These results are highly encouraging in light of the extremely challenging population, even among PDAC patients, in this study cohort," said Manuel Hidalgo, MD, PhD, Chief of the Division of Hematology and Medical Oncology and a Senior Member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, and principal investigator of this study. "All patients were initially diagnosed at stage IV, and greater than 70% had liver metastases, key contributing factors to very poor prognoses. I believe the results from this study strongly support further development."

"We are extremely pleased with these results, which demonstrate a meaningful improvement versus historical data across all study endpoints," stated Philip Serlin, Chief Executive Officer of BioLineRx. "The consistent improvement across all study endpoints represents a key differentiating factor relative to other compounds that showed improvement in only one endpoint in their initial studies and eventually failed in advanced studies. These positive results are further supported by a long-lasting median durability of clinical benefit of 5.6 months that we observed in this trial.

"Pancreatic cancer is one of the most difficult cancers to treat, with five-year survival rates of just 9% overall, and 3% for the greater-than-50% of patients initially diagnosed at stage IV. Therefore, even marginal improvements in survival endpoints in pivotal studies have been considered clinically meaningful and sufficient for regulatory approval. These positive efficacy results across all endpoints give us a high degree of confidence in their repeatability in a randomized trial and we plan to meet with the regulatory authorities in order to agree on the fastest pathway forward in this indication.

"In addition, we believe these results clearly support investigating the motixafortide/immune-checkpoint-inhibitor platform with other standard-of-care chemotherapies in earlier PDAC treatment lines, as well as in other ‘cold’ solid tumors. To that end, we are currently investigating motixafortide in combination with an anti-PD-1 and chemotherapy (gemcitabine and nab-paclitaxel) in first-line pancreatic cancer, and we are assessing potential combinations in other solid-tumor indications as well.

"These data are particularly exciting in light of the strikingly positive results of the interim analysis from our Phase 3 GENESIS study of motixafortide in stem cell mobilization that we recently announced in October. Motixafortide has now demonstrated clinical utility in two therapeutic areas through multiple mechanisms of action, supporting our belief that it can serve as the backbone of a number of promising combination therapies to treat a broad range of cancer types," Mr. Serlin concluded.

BioLineRx plans to present the full data set at an upcoming medical conference.

KOL Webinar Information
BioLineRx will host a KOL webinar today, December 16, 2020 at 8:00 a.m. EST. The webinar will feature presentations by Key Opinion Leaders (KOLs) Gulam Manji, M.D., Ph.D. (Columbia University Medical Center), Manuel Hidalgo, M.D., Ph.D. (Weill Cornell Medicine), and Talia Golan, M.D. (Sheba Medical Center), who will discuss the current treatment landscape and unmet medical need in treating patients with pancreatic cancer, and the COMBAT study data. BioLineRx’s management team will also discuss the COMBAT results. Drs. Hidalgo and Golan will be available to answer questions following the formal presentations.

Interested parties can register for the webinar here.

About COMBAT/KEYNOTE-202
The Phase 2a COMBAT/KEYNOTE-202 study was originally designed as an open-label, multinational, multicenter, single-arm trial to evaluate the safety, tolerability and efficacy of the dual combination of motixafortide and KEYTRUDA, an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in 37 subjects with metastatic pancreatic adenocarcinoma (2L-5L). The dual combination study was conducted under a clinical trial collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary, where MSD provided KEYTRUDA and BioLineRx was the study sponsor and owns all rights to motixafortide.

In July 2018, the Company announced the expansion of the collaboration with MSD to include a triple combination arm, as part of the COMBAT/KEYNOTE-202 study investigating the safety, tolerability and efficacy of motixafortide, KEYTRUDA and chemotherapy in 43 patients initially diagnosed with unresectable stage IV metastatic PDAC, who had progressed following first-line gemcitabine-based therapy. These results are being announced today.

The study was carried out primarily in the US, Spain and Israel.

About Motixafortide in Cancer Immunotherapy
Motixafortide is targeting CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including PDAC. CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and CXCR4 overexpression has been shown to be correlated with poor prognosis.

Motixafortide is a short synthetic peptide used as a platform for cancer immunotherapy with unique features allowing it to function as a best-in-class antagonist of CXCR4. It shows high-affinity, long receptor occupancy and acts as an inverse agonist.

In a number of clinical and preclinical studies, motixafortide has been shown to affect multiple modes of action in ‘cold’ tumors, including immune cell trafficking, tumor infiltration by immune effector T cells, and reduction in immunosuppressive cells (such as MDSCs) within the tumor microenvironment, turning ‘cold’ tumors, such as pancreatic cancer, into "hot" (i.e., sensitizing them to immune checkpoint inhibitors and chemotherapy).

About Pancreatic Cancer
Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. Its incidence rate in the US is estimated at 3.2% of new cancer cases. In 2018, approximately 450,000 individuals globally were diagnosed with this condition, 55,000 of them in the US; and the incidence of pancreatic cancer is expected to continue to increase. Symptoms are usually non-specific and as a result, pancreatic cancer is often not diagnosed until it reaches an advanced stage. Surgical resection does not offer adequate treatment since only 20% of patients have resectable tumors at the time of diagnosis. Even among patients who undergo resection for pancreatic cancer and have tumor-free margins, the five-year survival rate is only 10%-25%. The overall five-year survival rate among pancreatic cancer patients is 9%, which constitutes the highest mortality rate among solid tumor malignancies. The overall median survival is less than one year from diagnosis, highlighting the need for the development of new therapeutic options.

Despite advances in chemotherapeutics and immunotherapy, increases in median and overall survival rates in pancreatic cancer have been modest. Pancreatic cancer remains an area of unmet medical need, with no new approved therapies since the approval of nab-paclitaxel (Abraxane) in combination with gemcitabine for first-line treatment in 2013 and Onivyde in combination with fluorouracil and leucovorin for second-line treatment in 2015. The limited clinical benefits demonstrated by these existing standard treatment options reinforce the need for additional approaches.