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Codiak Presents First Preclinical Data for exoASO, Engineered Exosomes Designed to Reprogram Tumor-Associated Macrophages

On November 18, 2019 Codiak BioSciences, Inc., a company at the forefront of advancing engineered exosomes as a new class of biologic medicines, reported the first preclinical data for its engEx Platform program, exoASO. These data, which were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Special Conference on Tumor Immunology and Immunotherapy, demonstrate the potential of engineered exosomes incorporating an antisense oligonucleotide (ASO) to selectively reprogram tumor-associated macrophages and generate potent anti-tumor activity (Press release, Codiak Biosciences, NOV 18, 2019, View Source [SID1234551438]).

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"We continue to expand the therapeutic potential of engEx engineered exosomes and build our pipeline of novel biologics designed to target pathways that have been historically difficult to effectively or safely drug," said Douglas E. Williams, Ph.D., President and Chief Executive Officer of Codiak. "These data show us the utility of exoASO in both selectively targeting classically undruggable transcription factors and successfully reprogramming immunosuppressive macrophages, representing a potentially groundbreaking approach."

Highly immunosuppressive macrophages (M2 phenotype) are immune cells that are potent drivers of tumor growth by creating an immunesuppressive environment in the tumor. Utilizing its proprietary engEx Platform, Codiak developed engineered exosomes exogenously loaded with an ASO as part of its exoASO program. exoASO is designed to selectively deliver ASOs to M2 macrophages, targeting and decreasing the expression of the key immunosuppressive transcription factors, STAT6 and C/EBPβ.

Key conclusions from in vitro and in vivo preclinical studies demonstrate that exoASO effectively reprogrammed M2 macrophages to a pro-inflammatory M1 phenotype, promoting targeted anti-tumor activity. In vitro, exoASO was preferentially taken up by M2 macrophages to a significantly greater extent than free ASO, resulting in greater knockdown of STAT6 and C/EBPβ mRNA. Subsequent gene expression analysis and cytokine assays showed an up to 40-fold increase in TNFα and an up to 29-fold decrease in IL-10 associated with exoASO treatment, consistent with repolarization from immunosuppressive M2 macrophages to immune stimulatory M1 macrophages. In in vivo studies using a PD1-refractory mouse tumor model, both exoASO-STAT6 and exoASO-C/EBPβ showed significant anti-tumor growth inhibition as monotherapies, resulting in 50 percent and 60 percent complete responses, respectively, compared to no complete responses with free ASO. mRNA analysis of tumor samples examining expression of M2 and M1 cytokines was consistent with reprogrammed macrophages from the M2 to M1 phenotype.

Data from the poster titled "Reprogramming of tumor-associated M2 macrophages with antisense oligonucleotides-loaded exosomes results in potent single-agent antitumor activity" (A50) is available for download on the Codiak website.

About engEx Platform

The engEx Platform is Codiak’s proprietary exosome therapeutic engine for engineering and manufacturing novel exosome product candidates designed to target multiple pathways throughout the body. Using this platform, Codiak can design exosomes with precisely engineered properties, incorporate various types of biologically active molecules and direct them to specific cell types and tissues. These exosomes engage by cellular uptake, membrane-to-membrane interaction or a combination of both, and are designed to change the biological functioning of the recipient cells in order to produce the intended therapeutic effect. Codiak is building a broad pipeline of engEx product candidates that may have a transformative impact on the treatment of many diseases.

Sensei Biotherapeutics Announces First Patient Dosed in Phase 1/2 Clinical Trial of SNS-301 in Patients with ASPH-Positive Head and Neck Cancer

On November 18, 2019 Sensei Biotherapeutics, Inc., a clinical-stage biopharmaceutical company developing precision immuno-oncology therapies, reported the dosing of the first patient in its Phase 1/2 clinical trial evaluating SNS-301 in patients with ASPH‑positive head and neck cancer who have previously received immune checkpoint inhibitors (Press release, Sensei Biotherapeutics, NOV 18, 2019, View Source [SID1234551437]). SNS-301 is a first-in-class immunotherapy candidate utilizing a bacteriophage viral vector that targets human aspartate β‑hydroxylase (ASPH), and is the company’s first program to enter clinical development from its proprietary drug discovery platform.

The Phase 1/2 clinical trial is a multicenter, open-label trial designed to evaluate the safety, preliminary efficacy and immunogenicity of SNS-301 in combination with pembrolizumab. The study will include ASPH‑positive patients with locally advanced unresectable or metastatic/recurrent squamous cell head and neck cancer currently receiving pembrolizumab or nivolumab. Sensei expects to enroll approximately 30 patients in this two-stage trial with primary efficacy endpoints including objective response rate, duration of response, and multiple secondary endpoints measuring immune responses.

"We are pleased to advance SNS-301 into a Phase 1/2 clinical trial in head and neck cancer, an indication that continues to have a high unmet medical need. We have previously demonstrated dose-dependent ASPH-specific immunogenicity, encouraging clinical activity and a favorable safety profile in ASPH‑positive patients through proof-of-concept studies with SNS-301," said Ildiko Csiki, M.D., Ph.D., consulting Chief Medical Officer of Sensei Biotherapeutics. "Targeting ASPH represents a novel strategy for treating cancer and we believe that SNS-301 has potentially broad applicability across a wide variety of cancers with its unique mechanism combined with checkpoint inhibition. We look forward to providing preliminary results at a major medical meeting in 2020."

About SNS-301

SNS-301 is a first-in-class immunotherapy candidate utilizing a bacteriophage viral vector that targets human aspartate β-hydroxylase (ASPH), a cell surface enzyme that is normally expressed during fetal development. Expression of ASPH is upregulated in more than 20 different types of cancer and is related to cancer cell growth, invasiveness, and is inversely correlated with poor disease prognosis. SNS-301 is designed to overcome self-tolerance and induce robust and durable humoral and cellular immune responses that are specific to ASPH. SNS-301 is delivered through intradermal injection and avoids time consuming and uncomfortable infusions, greatly facilitating ease of use.

UroGen to Present at November 2019 Investor Conferences

On November 18, 2019 UroGen Pharma Ltd. (Nasdaq:URGN), a clinical-stage biopharmaceutical company developing treatments to address unmet needs in uro-oncology, reported that it will participate in fireside chats at the following conferences in November (Press release, UroGen Pharma, NOV 18, 2019, View Source [SID1234551436]):

Stifel 2019 Healthcare Conference

Tuesday, November 19th
2:25PM Eastern Time
New York, NY
Jefferies 2019 London Healthcare Conference

Wednesday, November 20th
4:00PM Greenwich Mean Time
London, UK
A live audio webcast of each event will be available on the Investors section of UroGen’s website, www.urogen.com. A replay of each webcast will be available on the website for approximately two weeks.

AgilVax to Present Positive Preclinical Data for Monoclonal Antibody Targeting xCT at the American Association for Cancer Research’s Tumor Immunology and Immunotherapy Conference

On November 18, 2019 AgilVax Inc., a biopharmaceutical company that discovers and develops targeted antibody-based therapeutics, reported that preclinical data describing M5, the Company’s monoclonal antibody targeting xCT, will be presented by Dr. Salameh at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Tumor Immunology and Immunotherapy Conference being held at the Boston Marriott Copley Place in Boston, MA (Press release, Agilvax, NOV 18, 2019, View Source [SID1234551435]).

Title:

Development of a monoclonal antibody targeting xCT/SLC7A11 expressed in metastatic cancer cells

Poster Session:

Poster Session B

Session Date:

Tuesday, November 19

Board Number (poster number):

B37

Time:

4:30 p.m. to 7:00 p.m.

Session Location:

Back Bay

"We are pleased with our continued progress on developing multiple solutions to target cancer cells overexpressing xCT and thrilled to have the opportunity to showcase our advancements in a poster presentation at such a prestigious meeting," said Dr. Joseph Patti, President and CEO of AgilVax. Dr. Patti further stated, "xCT overexpression occurs in several cancers leading to metabolic changes that reprograms cells for growth and progression. AgilVax’s antibody-based therapeutics have shown reduction of primary tumor formation and lung metastases illustrating the potential to create durable responses in patients suffering from colorectal and other metastatic cancers.

CarThera and KIYATEC Collaborate in Effort to Bring Personalized Medicine to Patients Stricken by Brain Cancer

On November 18, 2019 KIYATEC, Inc. and CarThera reported that they have entered into a clinical collaboration for the purpose of advancing innovation and improving treatments for patients diagnosed with glioblastoma, a highly aggressive form of brain cancer that afflicts more than 130,000 patients worldwide per year and is characterized by historically poor clinical outcomes (Press release, KIYATEC, NOV 18, 2019, View Source [SID1234551434]). The collaboration will focus on accelerating the development and validation of their emerging technologies to improve both the selection and effectiveness of drugs commonly recommended and used to treat the disease.

"Relevant clinical advances that improve outcomes for patients with glioblastoma have been few and far between over the last two decades," said Frederic Sottilini, CEO of CarThera. "Despite multimodal therapy, median survival remains around 15 months for these patients, virtually all of whom recur. Our goal is to optimize the selection and delivery of drug therapies to extend the lives of patients with glioblastoma."

The two companies were brought together by one of the world’s leading neuro-oncology and glioblastoma experts, John de Groot, M.D., professor and chairman ad interim, The University of Texas MD Anderson Cancer Center, who recognized the synergistic nature of their respective clinical initiatives. CarThera is currently conducting a multi-center clinical study of its novel ultrasound technology, SonoCloud-9, designed to increase the permeability of the blood brain barrier to improve the delivery of chemotherapeutic agents to the brains of patients with recurrent glioblastoma. KIYATEC is conducting a multi-center clinical study of its ex vivo 3D cell culture technology to accurately predict pre-treatment, patient-specific response to recommended standard of care cancer drugs for newly diagnosed and recurrent glioblastoma.

"As someone who cares for patients with glioblastoma, I applaud the efforts of CarThera and KIYATEC to bring evidence-based advances to the clinic for the purpose of improving outcomes for patients with glioblastoma," said Dr. de Groot. "I envision these two technologies as being complementary with the potential to transform the way in which neuro-oncologists manage glioblastoma patients."

Under the terms of the clinical collaboration, KIYATEC will conduct ex vivo drug response profiling on glioblastoma tissue samples from patients enrolled in CarThera’s clinical study. CarThera will benefit from having ex vivo drug response profiling for patients enrolled in its study, while KIYATEC will correlate its patient-specific, pre-treatment drug response predictions with actual clinical outcomes of patients in CarThera’s study. For both companies, this collaboration represents an opportunity to enrich their portfolios of clinical evidence with the goal of helping clinicians improve outcomes for their patients with glioblastoma.

"Both of our companies are dedicated to ensuring that glioblastoma patients receive the most appropriate drug therapy at the right time, and that the efficacy of that therapy is maximized to its fullest therapeutic potential," said Matthew Gevaert, CEO and co-founder of KIYATEC. "We believe that this clinical collaboration has the potential to help us accelerate and deliver on the long-awaited promise of personalized medicine for these deserving patients."

Both companies will be sending delegates to the 24th Annual Meeting of the Society for Neuro-Oncology, November 20-24 in Phoenix, Arizona.