On October 31, 2023 Leroy Hood, MD, PhD, co-founder of Seattle’s Institute for Systems Biology (ISB) and a pioneer in systems biology, and Rebecca Lambert, founder and CEO of NED Biosystems, Inc. (NED), a public benefit corporation that is developing the first oral "systems treatment" for cancer, reported to have entered into a memorandum of understanding to collaborate on a clinical trial to show how cancer’s onset may be reversed (Press release, NED Biosystems, OCT 30, 2023, View Source [SID1234636544]).

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NED’s cancer treatment, NED-170, takes a systems approach that combines repurposed, oral agents that are well documented in humans to affect critical cancer disease-driver processes at doses that lack customary toxicity and side effects.

"A systems biology approach is paramount – NED-170 is the multi-pronged treatment required to subvert cancer’s complex system," said Hood, who is inventor of the DNA Sequencer, technology which enabled the Human Genome Project.

The collaborative trial’s objective is to gather intelligence through a multi-dimensional monitoring of the tissue in which a tumor grows. A simple blood test utilizes the latest ultra-sensitive hyper-personalized proteomics technologies to measure the traces of more than 3,000 distinct proteins at once that reveal many processes in the tumor tissue, thereby offering an assessment of the specific efficacy of the individual agents in the multi-pronged approach.

NED-170’s Phase 1b/2 clinical trial is designed to treat patients concomitant to standard of care who lack an option for targeted therapy based on tumor genome sequencing in three indications representing large unmet needs: cholangiocarcinoma, triple negative breast cancer, and ovarian cancer.

NED is initially targeting the 50 percent to 80 percent of cancer patients whose tumors do not carry mutations for targeted therapy. Based on observational data, NED believes its systems treatment, when combined with standard of care therapies, may afford patients extended survival and enhanced quality of life. The data collected from NED’s initial trial and follow-on clinical trials will serve to develop a database for ISB’s large study utilizing proteomics and NED-170 to optimize the systems approach for suppression of cancer progression based on the driver processes in subclasses of patients.

"A truly comprehensive approach to a complex adaptive system like cancer, as the war on global terror has taught us, must be a multi-pronged approach that moderates, without adding stress, the various behaviors that promote cancer and allows the tissue to re-establish the balance of a normal cell community," said Sui Huang, MD, PhD, and ISB professor, cancer cell dynamics expert, and NED Biosystems Systems Advocate.

The envisioned high-dimensional profiling of a patient’s blood biochemistry baseline can inform doctors about how the tumor bed is preparing a tiny tumor for outgrowth before a tumor is clinically detectable, which can be different in different patients. It can also tell us precisely which biological processes a particular tumor relies on most to (re)grow in a given patient. Uncommon quality of life improvements (and cost savings) may be achieved when a cancer patient is treated with evidence-based agents efficacious against key pathways at doses that lack toxicity and side effects.

"By moderating multiple cancer progressing pathways and cancer stem cells at once, NED-170 affords a comprehensive systems approach never before available to cancer patients," said Lambert. "The comprehensive blood profiling utilized to measure NED-170’s impact on pathways advances a personalized measurement of each patient’s unique cancer signature."

On October 30, 2023 Enable Medicine, a leader in AI for biological research and drug discovery, reported that it will present a number of poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting being held November 1-5, 2023, in San Diego, California (Press release, Enable Medicine, OCT 30, 2023, View Source [SID1234636472]).

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"These study results will advance our understanding of the tumor microenvironment and empower researchers to use our comprehensive maps of disease biology to understand how the organization of cells impact disease pathology, progression, and therapeutic response."

Post this
Title: From images to insights: Deep spatial profiling reveals disease and treatment biomarkers
Abstract Number: #95
Date / Time: November 3rd, 12–1:30 p.m. PDT & November 4th, 11:55–1:25 p.m. PDT
Location: Exhibit Halls A and B1 – San Diego Convention Center

Title: Integrative spatial multi-omics analysis of NSCLC tumor microenvironment identifies key features associated with response to immune checkpoint inhibitor therapy
Abstract Number: #222
Date / Time: November 3rd, 12–1:30 p.m. PDT & November 4th, 11:55–1:25 p.m. PDT
Location: Exhibit Halls A and B1 – San Diego Convention Center

Poster presentation details:
Title: emObject: domain specific data abstraction for spatial omics
Abstract Number: #899
Date / Time: November 3rd, 12–1:30 p.m. PDT & November 4th, 11:55–1:25 p.m. PDT
Location: Exhibit Halls A and B1 – San Diego Convention Center

Title: Quantitative cell morphology featurization in multiplexed immunofluorescence images reveals tumor subtypes in cancer microenvironments
Abstract Number: #1290
Date / Time: November 3rd, 12–1:30 p.m. PDT & November 4th, 11:55–1:25 p.m. PDT
Location: Exhibit Halls A and B1 – San Diego Convention Center

Title: A machine learning toolkit for automated processing of multiplexed immunofluorescence images
Abstract Number: #1302
Date / Time: November 3rd, 12–1:30 p.m. PDT & November 4th, 11:55–1:25 p.m. PDT
Location: Exhibit Halls A and B1 – San Diego Convention Center

Title: Polarity measurements from multiplex imaging suggest immune cell activation
Abstract Number: #1314
Date / Time: November 3rd, 12–1:30 p.m. PDT & November 4th, 11:55–1:25 p.m. PDT
Location: Exhibit Halls A and B1 – San Diego Convention Center

Title: Identification and generalization of tissue structures with spatial cellular graph partitioning
Abstract Number: #1315
Date / Time: November 3rd, 12–1:30 p.m. PDT & November 4th, 11:55–1:25 p.m. PDT
Location: Exhibit Halls A and B1 – San Diego Convention Center

"We are excited to showcase the capabilities of Enable Medicine’s platform in analyzing pathology and other omic data to improve our understanding of cancer biology and predict potential treatment response in patients," said Sunil Bodapati, CEO, Enable Medicine. "These study results will advance our understanding of the tumor microenvironment and empower researchers to use our comprehensive maps of disease biology to understand how the organization of cells impact disease pathology, progression, and therapeutic response."

The full abstracts will be released on the SITC (Free SITC Whitepaper) website on Tuesday, October 31, 2023 at 9:00 a.m. ET.

On October 30, 2023 Sonata Therapeutics, Inc., a biotechnology company developing a new class of therapeutics called Network Medicines, reported that it will be presenting three posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Sonata Therapeutics, OCT 30, 2023, View Source [SID1234636471]).

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Network Medicines are drugs designed to modulate all the key cell types in networks of multifactorial diseases, thereby to halt or potentially reverse damage caused by such diseases. The majority of medicines are designed to disrupt or enhance single pathways in order to stop disease progression, but this approach often requires additional medications that target a different pathway, or combination therapy, to prevent drug resistance or drive response. In contrast, Sonata’s Network Medicines target pathways that change the complete dynamics of multifactorial diseases, resulting in more durable therapeutics and potentially better outcomes for patients.

One of the poster presentations will highlight one of Sonata’s Network Medicines, iART, that reprograms diseased cells to become the coordinators of cure for various indications including cancer. This Network Medicine has demonstrated profound efficacy across a variety of tumor models, representing an exclusive, broadly applicable off-the-shelf therapy for use in oncology.

The second poster presentation will highlight how SNT-20109, one of Sonata’s lead oncology programs, can induce protective immunity and an innovative form of enhanced-immunogenic cell death that has never been characterized in murine cancer models.

The third poster presentation will highlight SNT-4288, another of Sonata’s lead oncology programs, as a novel tool to induce ferroptosis for the treatment of sarcoma.

"As the former President of SITC (Free SITC Whitepaper), I’m thrilled to be back at the organization’s annual meeting as a member of Sonata’s leadership team and showcasing our novel Network Medicines approach that reprograms diseased cells to release curative signals resulting in durable disease resolution," said Francesco Marincola, M.D., Chief Scientific Officer of Sonata. "I look forward to connecting with my fellow leaders in the field of immuno-oncology and discussing the exciting potential of Sonata’s platform and programs."

The accepted abstracts are available online through the SITC (Free SITC Whitepaper) conference website: View Source

In addition, Dr. Marincola will co-chair the symposium "Synthetic Biology – Cell Therapy for Patients with Solid Cancer" on Friday, November 3 from 12:15-1:15 pm PT in Room 11AB of the conference venue. The symposium, sponsored by the Champalimaud Foundation, will highlight real-world challenges, outline solutions and foster collaborations to achieve the ultimate goal of significantly improving the survival of patients with cancer through synthetic biology.

Poster Presentations

Title: Sonata’s Proprietary Intrinsic Antigen Release Technology (iART) Drives In Situ Generation of Potent Anti-Tumor Immunity Across Warm and Cold Tumor Models
Date/Time: Friday, November 3, 2023, 12:00pm-1:30pm and 5:10pm-6:40pm PT
Abstract Number: 1403-B
Location: Ground Level, Exhibit Halls A and B1, San Diego Convention Center
Presenter: Ryan Shaler, Ph.D.

Title: SNT-20109 Induces Protective Immunity in the Murine Syngeneic Tumor Cell Line, CT26: A Dual Approach of Direct Cytotoxicity and Defined Immune Activation
Date/Time: Friday, November 3, 2023, 12:00pm-1:30pm and 5:10pm-6:40pm PT
Abstract Number: 1387
Location: Ground Level, Exhibit Halls A and B1, San Diego Convention Center
Presenter: Ryan Shaler, Ph.D.

Title: Exploring Novel Ferroptosis Inducer as a Promising Strategy for Sarcoma Treatment
Date/Time: Saturday, November 4, 2023, 9:00am-8:30pm PT
Abstract Number: 1442
Location: Ground Level, Exhibit Hall B, San Diego Convention Center
Presenter: Maria Cristina Munteanu, Ph.D.

On October 30, 2023 AnHeart Therapeutics ("AnHeart"), a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer, reported that it has entered into an exclusive license agreement with Nippon Kayaku Co., Ltd ("Nippon Kayaku") to market and distribute AnHeart’s lead investigational therapy, taletrectinib, in Japan (Press release, AnHeart Therapeutics, OCT 30, 2023, View Source [SID1234636470]). Taletrectinib is a next-generation ROS1 tyrosine kinase inhibitor (TKI) being developed for the treatment of ROS1-positive non-small cell lung cancer (NSCLC).

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Under the terms of the agreement, AnHeart will receive an upfront payment of $40 million and is entitled to potential regulatory and sales milestone payments and royalties based on annual net sales of taletrectinib in Japan. Nippon Kayaku will be responsible for regulatory approvals and commercialization of taletrectinib for ROS1-positive NSCLC in Japan, and will have rights to further develop taletrectinib for new indications in the region. AnHeart will be responsible for the clinical development of taletrectinib for ROS1-positive NSCLC and for supplying taletrectinib to Nippon Kayaku for future commercialization purposes in Japan.

AnHeart has reported positive data from two Phase 2 trials in 2023 showing taletrectinib has the potential to be a best-in-class therapy for people with ROS1-positive NSCLC, an underserved group of lung cancer patients in great need of new options. In both trials, interim results showed taletrectinib shrank tumors in more than 90% of patients with ROS1-positive NSCLC who had not previously received a ROS1 TKI (TKI naïve) and more than 50% of patients who had previously received a ROS1 TKI (TKI pre-treated), and responses were durable. Taletrectinib was generally well tolerated with a low incidence of neurological adverse events.

"We are excited to partner with Nippon Kayaku and look forward to working with a leading oncology company to bring taletrectinib to people with ROS1-positive NSCLC living in Japan," said Jerry Wang, PhD, Chief Executive Officer of AnHeart. "We have strategically selected partners across Asia to support our efforts to further develop and commercialize taletrectinib in the region. With the recently reported positive interim data from our global pivotal TRUST-II trial, we are well on our way to realizing our vision of bringing people with ROS1-positive NSCLC a new option."

About Taletrectinib

Taletrectinib is an oral, potent, brain penetrant, selective, next-generation potential best-in-class ROS1 inhibitor being evaluated for the treatment of ROS1-positive NSCLC.

AnHeart is evaluating taletrectinib in ROS1-positive NSCLC patients in two Phase 2 trials, TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global pivotal trial.

At the recent European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023, AnHeart reported positive interim results from the global pivotal TRUST-II trial showing a confirmed objective response rate (cORR) as assessed by independent review committee (IRC) of 92% in ROS1 TKI naïve patients (n=25) and 57% in patients previously treated with a ROS1 TKI (n=21). Taletrectinib also showed robust intracranial activity in the subgroup of patients with disease that had spread to the brain (80% intracranial ORR in TKI naïve patients, n=5; 63% intracranial ORR in TKI pre-treated patients, n=8). Median progression-free survival (IRC-assessed) was not reached for TKI naïve patients and was 11.7 months for TKI pre-treated patients.

Earlier this year, AnHeart reported data from the TRUST-I trial in China, which showed a cORR of 93% in ROS1 TKI naïve patients (n=67) and 53% in crizotinib pre-treated patients (n=38), as assessed by IRC. A pooled analysis of TRUST-I and Phase 1 trials with taletrectinib showed median progression-free survival of 33.2 months and 11.8 months in ROS1 TKI naïve and crizotinib pre-treated patients, respectively.

Across all trials to date, taletrectinib has generally been well tolerated. The most common treatment emergent adverse events (TEAEs) have been increased liver enzymes and gastrointestinal-related adverse events, the majority of which were Grade 1 or Grade 2. Incidence of neurological TEAEs were low; the most common was dizziness (19%), most of which was Grade 1.

About ROS1-Positive NSCLC

More than one million people are anticipated to be diagnosed with NSCLC, the most common form of lung cancer, in the United States, Europe, China and Japan in 2023. It is estimated that approximately 1-2% of people with NSCLC in western countries and approximately 3% in China are ROS1-positive, meaning more than 22,000 people will be diagnosed with ROS1-positive NSCLC in these regions in 2023. There are two FDA approved first-generation TKIs for people with newly diagnosed advanced or metastatic ROS1-positive NSCLC and no FDA approved therapies for people whose ROS1-positive NSCLC has progressed following treatment with these medicines. Up to 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain (brain metastases), increasing up to 55% for those whose cancer has progressed following initial treatment.

On October 30, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA), a clinical stage company developing telomere-targeting immunotherapies for cancer, reported positive results from an investigational new drug-enabling study of the Company’s second-generation telomere-targeting agents derived from lipid-modified THIO molecules (Press release, MAIA Biotechnology, OCT 30, 2023, View Source [SID1234636469]). MAIA’s second-generation telomere-targeting molecule program seeks to discover new compounds with improved specificity towards cancer cells relative to normal cells, potentially increased anticancer activity, and stronger chemistry manufacturing control characteristics.

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"In this study we demonstrated broad-spectrum therapeutically-attractive opportunities for specific telomeric stress-inducing treatments. The results demonstrate an increase in innate sensing and adaptive antitumor immunity via the self-produced chemical modification of cancer cell telomeres by THIO," said MAIA’s Chief Scientific Officer Sergei Gryaznov, Ph.D.

The new THIO prodrugs are lipid conjugated compounds derived from THIO. The prodrugs are pharmacologically inactive compounds that, after intake, are metabolized into a pharmacologically active drug. In vitro, these compounds were able to induce telomeric DNA damage responses that were similar or more profound than those for THIO, as assessed by quantitative Telomere Damage Induced Foci assays (TIF formation). Efficient formation of micronuclei structures was also observed. Initial in vivo evaluation of the anticancer activity, conducted in human xenografts and murine syngeneic models of colorectal cancer, demonstrated potent anticancer activity at relatively low dose levels for one of the lead lipid conjugates.

"Our findings from this study demonstrate the significance of telomeric DNA structural and functional integrity for cancer cell survival. The high potency of these THIO-like agents warrants further in vivo in-depth investigation as a potential next generation of telomerase-mediated telomere-targeting compounds," said Vlad Vitoc, M.D., MAIA’s Chief Executive Officer.

The findings were presented by Dr. Gryaznov at the International Biochemistry Congress 2023, organized by the Turkish Biochemical Society and held in Turkey. The findings are detailed in the abstract available in the event website under Speakers, Sergei M. Gryaznov and Lecture Abstract sections.

The telomere-centric action of MAIA’s lead candidate THIO is being evaluated in Phase 2 clinical trials (THIO-101) in non-small-cell lung carcinoma (NSCLC) patients.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.