On March 31, 2021 Boundless Bio, a next-generation precision oncology company developing innovative therapeutics directed against extrachromosomal DNA (ecDNA) in aggressive cancers, reported plans to present at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, held virtually from April 10-15, 2021 (Press release, Boundless Bio, MAR 31, 2021, View Source [SID1234577453]). The poster presentation will show how ecDNA mediates resistance to targeted therapy via oncogene switching and will highlight the urgent need to develop innovative new therapeutic approaches for gene amplified tumors that are driven by ecDNA.

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Presentation details:

Title: Extrachromosomal DNA (ecDNA)-driven switching of oncogene dependency facilitates resistance to targeted therapy
Session Title: Drug Resistance in Molecular Target Therapeutics
Session Category: PO.ET03.01
Abstract Number: 1089
Date and Time: April 10, 2021, 8:30 a.m. – 11:59 p.m. ET

About ecDNA

Extrachromosomal DNA, or ecDNA, are distinct circular units of DNA lacking centromeres but containing functional genes, including oncogenes, that are separated from tumor cell chromosomes. ecDNA replicate within cancer cells and can be passed to daughter cells asymmetrically during cell division, thereby constituting a primary driver of focal gene amplification and copy number heterogeneity in cancer. By leveraging the plasticity afforded by ecDNA, cancer has the ability to increase or decrease copy number of select oncogenes located on ecDNA to enable survival under selective pressures, including chemotherapy, targeted therapy, immunotherapy, or radiation, making ecDNA one of cancer cells’ primary mechanisms of recurrence and treatment resistance. ecDNA are not found in healthy cells but are present in many solid tumor cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes.

On March 31, 2021 Affimed N.V. (NASDAQ: AFMD), a clinical-stage immuno-oncology company, and NKMax America Inc., a clinical stage biotech company, reported that the U.S. Food and Drug Administration (FDA) cleared an investigational new drug application (IND) for an Affimed and NKMax America co-sponsored Phase 1/2a dose escalation and expansion study in which the two companies will investigate the combination of AFM24, an EGFR/CD16A innate cell engager (ICE), and SNK-01, an autologous NK-cell product, in patients suffering from tumors known to express EGFR (Press release, NKGEN Biotech, MAR 31, 2021, View Source [SID1234578705]). The combination represents a novel approach to exploring innate immunity-based therapeutics to treat patients with solid tumors who failed conventional therapy with the aim to improve outcomes for high-medical need patient populations.

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"This combination is part of our overall development strategy for AFM24, the first and only innate cell engager in clinical development for solid tumors. In addition to NK cell-based combinations, we are also developing AFM24 as single agent and in combination with atezolizumab in several tumor indications," said Dr. Andreas Harstrick, Affimed’s Chief Medical Officer. "The mechanism of action of the two compounds could be highly synergistic as AFM24 has strong binding affinity to NK cells, directing them to kill tumor cells. Moreover, this combination approach represents an opportunity to supplement patients with dysregulated innate immune systems with targeted cellular therapy."

"The FDA clearance of our IND application for SNK-01 in combination with AFM24 is an important milestone for our Natural Killer cell therapy development program," said Stephen Chen, Chief Operating Officer and Chief Technical Officer of NKMax America. "We look forward to investigating this combination as part of our comprehensive strategy aimed at producing a cell therapy for patients with advanced/metastatic EGFR-expressing cancers."

Further Information About the AFM24/SNK-01 Phase 1/2a study

The Phase 1/2a study is based on preclinical in vitro testing, combining Affimed’s ICE AFM24 with NKMax America autologous NK-cell product SNK-01, which showed enhanced activity of NK cell induced target cell killing. The Phase 1/2a study will be an open-label, non-randomized, multi-center, US only, dose escalation trial to evaluate the combination in adult patients with EGFR-expressing tumors. The primary objective of the phase 1 study part will be to establish the safety and the recommended phase 2 dose of AFM24/SNK-01 combination, as well as to evaluate pharmacokinetics, pharmacodynamics, and preliminary activity in patients with advanced cancers expressing EGFR. The phase 2a portion of the study will evaluate the preliminary efficacy of AFM24 in patients with select solid tumor subtypes.

On March 31, 2021 Hwasun Chonnam National University Hospital and a bio venture company founded by the hospital’s medical staff are joining hands to accelerate the development of radioactive pharmaceuticals for cancer diagnosis and treatment. Hwasun Chonnam National University Hospital recently signed an MOU with CNCure Co., Ltd (Press release, Hwasun Chonnam National University Hospital, MAR 31, 2021, View Source [SID1234649031]).

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Through this business agreement, the two organizations promised to cooperate and exchange information on the development of radiopharmaceuticals and the progress of clinical trials, cooperate in the use of in-house GMP facilities for the production of radiopharmaceuticals for clinical trials, and share medical and pharmaceutical academic knowledge and information necessary for conducting clinical studies.

C&Cure Co., Ltd. is a bio venture company established in 2019 by the medical staff of Hwasun Chonnam National University Hospital and researchers from Chonnam National University College of Medicine.

The main business is the development of cancer-targeting bacteria-based anticancer treatment, and the development of radiopharmaceuticals for the diagnosis and treatment of infectious diseases and cancer. As of now, 8.8 billion won in private investment and 1 billion won in government-local government research projects have been secured. Clinical trials of two types of radiopharmaceuticals for the diagnosis of cancer and infectious diseases are scheduled to begin this year.

Professor Min Jeong-jun, the CEO, is also the president of the Korean Society of Nuclear Medicine and is a world authority in the field of theranostics, which performs imaging diagnosis and treatment simultaneously.

He has developed the world’s first drug-releasing Salmonella and E. coli, opening a new horizon in cancer treatment technology. He has also developed radioactive medicines that can precisely attack malignant melanoma, lung cancer, and colon cancer. While leading the Molecular Imaging Theranostics Research Institute, he has published over 200 papers domestically and internationally, and holds dozens of patents in related fields.

CEO Min said, "I am reassured that we have been able to collaborate on research and development with Hwasun Chonnam National University Hospital, which is leading the next-generation medical care and conquering cancer," and added, "We will join forces to accelerate the development of radioactive pharmaceuticals as well as personalized precision cancer treatment for patients."

President Shin Myeong-geun responded, "Like ‘Vaccell Bio,’ which was founded in 2010 by some of our medical staff and is making a name for itself in the development of anticancer immune cell therapy, the establishment of a venture company can be a catalyst for strengthening our clinical treatment capabilities and medical competitiveness." He added, "We will do our best to enable more efficient cancer diagnosis and treatment through strong industry-hospital cooperation."

On March 31, 2021 Outpace Bio, a biotechnology company building a platform to create next-generation smart cell therapies, reported the closing of a $30 million Series A financing round (Press release, Outpace Bio, MAR 31, 2021, View Source [SID1234637769]). The oversubscribed financing was led by ARTIS Ventures and Lyell Immunopharma, Inc., with additional participation from Abstract Ventures, Civilization Ventures, Mubadala Capital (the asset management arm of Mubadala Investment Company), Playground Global, Sahsen Ventures, and WRF Capital. Funding will be used to demonstrate proof of principle for Outpace’s platform. In addition to closing the financing round, Outpace has entered into a collaboration with Lyell Immunopharma for joint research and subsequent development and commercialization by Lyell of a potential immune cell therapy for the treatment of cancer.

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Creating next-generation smart cell therapies

Certain diseases have remained incurable despite decades of effort because they are too complex for any single molecule to solve. Outpace is building a platform to improve the safety and efficacy of cell and gene-based therapies.

"Diseases like cancer and autoimmunity happen when cells default to the wrong decisions. A biological activity that is beneficial in one context can drive dysfunction or toxicity in another. Outpace is working to overcome this by reprogramming cells to make the right decisions in the right context," said Marc Lajoie, CEO and co-founder of Outpace. "We believe that cures will require the full power of cells to intervene in complex biology in ways that small molecule drugs and biologics cannot."

Just as custom-designed software and hardware have enabled modern smartphones to revolutionize how people interact with information, Outpace custom-designs biological software and hardware to revolutionize how cells interact with disease. Outpace’s built-for-purpose proteins unlock biological functions that off-the-shelf parts cannot. Initial proof points are focused on creating highly functional, ultra-specific T cell therapies that will be effective against solid tumors, while also laying the groundwork to solve similar problems across the cell and gene therapy field.

"Outpace creates a unique opportunity to drive efficacy in cell and gene therapies without compromising on safety. The way to do that is by engineering new biology that can’t be achieved by repurposing nature – custom-designed proteins provide a unique opportunity to address specific therapeutic needs," said Vasudev Bailey, PhD, senior partner at ARTIS Ventures. "We believe the Outpace team has the knowledge and passion to revolutionize this field in close collaboration with other pharma and biotech leaders."

Outpace and Lyell to supercharge anticancer T cell therapies

Under the collaboration agreement, Outpace and Lyell will use Outpace’s technologies in an effort to unlock the biology of a cytokine that the companies believe has the potential to dramatically improve efficacy in treating patients with cancer, but would require careful control to avoid systemic toxicity.

"Outpace’s technology holds promise to enable the efficacy of this cytokine without the toxicity," said Rick Klausner, founder and executive chairman of Lyell. "Outpace’s approach is unique in its ability to directly modulate this biology, and we look forward to working with them."

The collaboration enables Outpace to combine its mechanism-driven approach to reprogramming biological function with Lyell’s translation expertise and deep mechanistic understanding of biology. Outpace plans to forge additional partnerships with other industry leaders to bring cell and gene therapies to the clinic, leveraging its platform to accelerate the development of new cures.

On March 31, 2021 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the European Commission (EC) has approved Cabometyx (cabozantinib) in combination with Bristol Myers Squibb’s Opdivo (nivolumab) for the first-line treatment of advanced renal cell carcinoma (aRCC) (Press release, Ipsen, MAR 31, 2021, View Source [SID1234577383]). This decision marks the first approval for Cabometyx in combination with another therapy in Europe and the third indication of Cabometyx in renal cell carcinoma (RCC).

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"Today’s EC approval for the use of Cabometyx in combination with Opdivo provides an important new first-line treatment option for patients living with advanced renal cell carcinoma," said Howard Mayer, Executive Vice President and Head of Research and Development, Ipsen. "At Ipsen, we’re proud that this, now approved, treatment option not only addresses key efficacy benefits, but also the need to maintain quality of life for patients. We look forward to collaborating with a broad range of European stakeholders to bring this unique combination to eligible patients living with advanced renal cell carcinoma."

The EC approval is based on results from the pivotal Phase III CheckMate -9ER trial, presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 and published in the New England Journal of Medicine (NEJM) on 3 March 2021. In the trial, Cabometyx in combination with Opdivo demonstrated significant improvements across all efficacy endpoints. In patients receiving the combination, median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months vs. 8.3 months respectively (HR: 0.51; 95% CI: 0.41–0.64; p<0.0001).1 Overall survival (OS) also demonstrated statistically significant improvements, reducing the risk of death by 40% versus sunitinib (HR: 0.60 [98.89% CI: 0.40-0.89]; p=0.001; median OS not reached in either arm).1 In addition, Cabometyx in combination with Opdivo demonstrated a superior objective response rate (ORR), with twice as many patients responding compared to sunitinib (55.7% vs. 27.1%; p<0.0001) and 8.0% vs. 4.6% achieved a complete response respectively.1 Key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-L1 subgroups.1 The combination was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor components in first-line aRCC.1

Additional data from the CheckMate -9ER trial were also presented in February at the recent American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Genitourinary Cancers Symposium (ASCO GU). These data highlighted sustained superior efficacy of Cabometyx in combination with Opdivo versus sunitinib for the first-line treatment of aRCC with a median follow-up of 23.5 months, as well as data suggesting significantly improved health-related quality of life (HRQoL) outcomes for the combination versus sunitinib.2,3 These HRQoL data, also included as part of the recently published NEJM publication, demonstrated that the combination was associated with a lower treatment burden, a decline in the risk of confirmed deterioration in HRQoL and a reduction of disease-related symptoms compared to sunitinib.1,3

"The combination of nivolumab and cabozantinib pairs two proven agents for advanced renal cell carcinoma that together have shown superior efficacy across key endpoints and subgroups of patients compared to sunitinib in the CheckMate -9ER trial. Additionally, the combination’s safety profile was manageable with known protocols, leading to a low rate of treatment-related discontinuations," said Marc- Oliver Grimm, M.D., Professor of Medicine and Urology Department Head, Jena University Hospital. "With today’s approval, clinicians in the EU will be able to offer patients with advanced renal cell carcinoma an additional combination therapy that may help them achieve early control of their disease and improve survival outcomes."

This approval allows for the marketing of Cabometyx in combination with Opdivo in this indication in all 27 member states of the European Union, Norway, Liechtenstein and Iceland. The U.S. Food and Drug administration approved Cabometyx for patients with aRCC as a first-line treatment in combination with Opdivo in January 2021.

Ipsen thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

About renal cell carcinoma
There are over 400,000 new cases of kidney cancer diagnosed worldwide each year.4 Of these, renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for approximately 90% of cases.5,6 It is twice as common in men, and male patients account for over two thirds of deaths.4 If detected in the early stages, the five-year survival rate is high, but for patients with advanced or late- stage metastatic RCC the survival rate is much lower, around 12%, with no identified cure for this disease.7,8

About the CheckMate -9ER trial
CheckMate -9ER is an open-label, randomized, multi-national Phase III trial evaluating patients with previously untreated advanced or metastatic RCC. A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to Cabometyx plus Opdivo (n= 323) versus sunitinib (n= 328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination versus sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About Cabometyx (cabozantinib)
Cabometyx is currently approved in 57 countries, including in the European Union, the U.K., Norway, Iceland, Liechtenstein, Australia, New Zealand, Switzerland, South Korea, Canada, Brazil, Taiwan, Hong- Kong, Singapore, Macau, Jordan, Lebanon, Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia, Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic, Ecuador and Thailand for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union, the U.K., Liechtenstein, Norway, Iceland, Canada, Australia, Brazil, Taiwan, Hong Kong, Singapore, Lebanon, Jordan, Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic, Ecuador and Thailand for previously untreated intermediate- or poor-risk advanced RCC; and in the European Union, the U.K., Liechtenstein, Norway, Iceland, Canada, Australia, Switzerland, Saudi Arabia, Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, Russian Federation, Ukraine, Turkey, Lebanon, United Arab Emirates, Peru, Panama, Guatemala, Chile, Dominican Republic, Ecuador and Thailand for HCC in adults who have previously been treated with sorafenib.

The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (SmPC) and in the U.S. Prescribing Information (PI).

Cabometyx is marketed by Exelixis, Inc. in the United States and by Takeda Pharmaceutical Company Limited in Japan. Ipsen has exclusive rights for the commercialization of Cabometyx outside of the U.S. and Japan. Cabometyx is a registered trademark of Exelixis, Inc.