On April 9, 2024 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported an update on its Phase 1 first-in-human study of OBX-115 tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced or metastatic melanoma, including 25-week median study follow-up safety data and newly detailed efficacy data, during a presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, CA (Press release, Obsidian Therapeutics, APR 9, 2024, View Source [SID1234641965]). The poster, "OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy induced deepening and durable responses without interleukin 2 (IL2) in patients with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma," was presented by Rodabe N. Amaria, M.D., professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and principal investigator of the study.

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The single-center study (NCT05470283) is evaluating the safety, tolerability, dosing, and efficacy of OBX-115 in patients with ICI-resistant metastatic melanoma. All 6 patients had disease that was primary-resistant to anti–PD-1 therapy, with a median of 2.5 (range, 1–5) lines of prior therapy.

OBX-115 was well-tolerated with a differentiated safety profile from non-engineered TIL cell therapy, which utilizes high-dose IL2:

No dose-limiting toxicities were observed
No Grade 4 or higher non-hematologic events were reported and 2 patients experienced limited Grade 3 events
No confirmed events of cytokine release syndrome, capillary leak syndrome, or ICANS were reported
OBX-115 induced consistently deepening and durable responses:

50% objective response rate and 33% complete response rate using investigator-assessed RECIST 1.1 criteria
All patients experienced tumor burden reduction and meaningful disease control for ≥12 weeks after infusion
All patients were alive and median PFS had not been reached, with 6-month PFS of 67%
Dr. Amaria stated, "The clinical safety and efficacy data from the first 6 patients treated with OBX-115 are promising and demonstrate a meaningful objective response rate. The results are particularly encouraging since OBX-115 is the first engineered TIL cell therapy not requiring IL2 co-administration. OBX-115 has the potential to drive durable responses in patients with ICI-resistant metastatic melanoma, without the well-described toxicity associated with IL2."

"We are highly encouraged by the promising OBX-115 data being shared today, which not only clinically validate Obsidian’s cytoDRiVE technology, but also demonstrate that OBX-115, with its positively differentiated safety profile, has the potential to further expand eligibility for TIL cell therapy and comprehensively address the unmet need in ICI-resistant advanced melanoma," commented Parameswaran Hari, M.D., Chief Development Officer of Obsidian.

In addition to the first-in-human study, Obsidian is actively enrolling patients with metastatic melanoma and NSCLC at multiple sites in its ongoing Phase 1/2 multicenter study. Additional details may be found at clinicaltrials.gov, using identifier: NCT06060613.

Obsidian also has 3 other poster presentations at AACR (Free AACR Whitepaper) 2024:

Title: Trial in progress: A Phase 1/2 study to investigate the safety and efficacy of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma
Presenting Author: Sajeve S Thomas, Orlando Health Cancer Institute, Orlando, FL

Title: Tumor-infiltrating lymphocytes (TIL) engineered with membrane-bound IL15 (cytoTIL15 cells) exhibit pharmacologically regulatable signal transduction in cis and trans
Presenting Author: Rachel Burga, Obsidian Therapeutics, Inc., Cambridge, MA

Title: Tumor-infiltrating lymphocytes (TIL) engineered with regulatable membrane-bound IL15 (mbIL15) and LIGHT (TNFSF14) show enhanced efficacy in fibroblast-containing cold tumors
Presenting Author: Balazs Koscso, Obsidian Therapeutics, Inc., Cambridge, MA

About OBX-115

Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. OBX-115 is being investigated in 2 ongoing and enrolling clinical trials in advanced or metastatic melanoma and NSCLC (NCT05470283 and NCT06060613).

On April 9, 2024 AffyImmune, a clinical-stage biopharmaceutical company committed to developing novel, first-in-class, affinity-tuned CAR T cell therapies, reported preclinical data on new indications for its lead program, AIC100, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (Press release, AffyImmune Therapeutics, APR 9, 2024, View Source [SID1234641964]). The data showcases the efficacy of AIC100 in non-small cell lung cancer (NSCLC) and cervical cancer in preclinical models expressing cell surface ICAM-1.

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Affinity tuned AIC100 is expected to selectively bind and kill tumor cells expressing cell surface ICAM-1 while sparing healthy cells.

The preclinical studies demonstrated that AIC100 exhibited potent cytotoxic activity against ICAM-1-positive NSCLC and cervical cancer cell lines in vitro, resulting in 100% cell death within 72 hours. The investigational affinity-tuned CAR T candidate AIC100 also demonstrated remarkable efficacy in NSCLC and cervical cancer xenograft models, with the active arm showing a significant reduction in tumor size and an increase in survival compared to placebo.

"We are excited to share preclinical proof-of-concept data for our affinity-tuned CAR T program AIC100 in new solid tumor types. Advanced stage cervical cancer and NSCLC represent significant unmet medical needs, with patients experiencing poor outcomes and a 5-year survival rate ranging from approximately 10 to 20%," said Matt Britz, CEO, AffyImmune. "These preclinical data build on the potential for AIC100 to be a first-in-class targeted therapy for ICAM-1-positive solid tumors with significant unmet medical need."

"Advanced lung and cervical cancers continue to have unmet medical need despite our recent advances in targeted and immune therapy. There are few good options for patients who experience progression after initial therapy for metastatic disease," said Jorge J. Nieva, MD, Associate Professor of Clinical Medicine, Keck School of Medicine, University of Southern California. "This promising preclinical data presented at AACR (Free AACR Whitepaper) 2024 suggest that AIC100 could be a potential new option for patients with these ICAM-1-positive tumors."

AIC100 is currently in Phase 1 trials for anaplastic and poorly differentiated thyroid cancer (NCT04420754).

On April 9, 2024 SimBioSys, a pioneering TechBio company unlocking the power of spatial biophysics with artificial intelligence (AI) and computational modeling to redefine precision medicine for cancer, reported the launch of its second clinical application TumorSight Plan – the first clinical decision support application to provide a data-driven approach to surgical planning for over 270,000 patients annually diagnosed with early-stage breast cancer in the U.S (Press release, SimBioSys, APR 9, 2024, View Source [SID1234641963]).

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Surgery is the first and most important line of treatment for nearly all patients with early-stage breast cancer, yet surgeons unfortunately lack tools to be more precise in their treatment planning decisions. The uncertainty surrounding the complete removal of each patient’s tumor and achieving an ideal cosmetic result often nudges decision-making towards mastectomy as the preferred choice over breast-conserving surgery.

Now, with TumorSight Plan, surgeons are empowered with visualization, data-driven insights, and best-practices to help support more effective provider-patient interactions and individualize treatment planning to right-size care. TumorSight Plan is powered by the FDA-cleared TumorSight Viz, an innovative 3D visualization solution to support the rapidly increasing use of MRI imaging in Breast Cancer. Both TumorSight Plan and Viz are now available to breast surgeons across the country and will be on display at the American Association of Breast Surgeon’s conference in Orlando from April 11th to 13th.

"Until now the decision about what was best, or even possible, for each patient was not always clear. SimBioSys’ TumorSight suite is a huge breakthrough in our capacity to utilize AI to calibrate a balance between decision standardization and individualized medicine. SimBioSys is leading breast surgeons and patients into an era of greater confidence in personalized decision making," said Dr. Christy Teal, Director of Breast Care Center and the Chief of Breast Surgery at GW Medical. Dr. Teal is also a renowned co-author of "No Longer Radical. Understanding Mastectomies and Choosing the Breast Cancer Care That’s Right For You."

SimBioSys is dedicated to expanding the TumorSight platform, with plans to incorporate additional innovative tools across surgical planning, risk assessment, treatment selection and precision dosing. This comprehensive approach aims to deliver holistic support for the cancer care journey, epitomizing the promise of true precision medicine.

"The reality is that the operation a woman has for breast cancer is often more dependent on the surgeon they see rather than their intrinsic disease due to lack of data-driven tools and approaches," said Barry Rosen, MD, CMO of SimBioSys and breast surgical oncologist. "Working with top surgeons across the United States, we now can harness the power of AI to make surgical planning more of a science than an art. TumorSight Plan gives the breast cancer surgeon a platform and opportunity to enable more analytical patient-centric decision making which should lead to higher percentage of women undergoing breast conservation surgery."

On April 9, 2024 Genialis, the RNA-biomarker company, reported a poster on a new AI/ML classifier, Genialis krasID, that accurately predicts clinical benefit in a real-world cohort of patients who received sotorasib, a KRAS inhibitor currently approved for KRAS G12C non-small cell lung cancers (Press release, Genialis, APR 9, 2024, View Source [SID1234641962]). Genialis presented additional findings on the performance of the biomarker in predicting drug response across preclinical models and real-world clinical benefit at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2024 Annual Meeting in San Diego on April 5-10, 2024.

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Genialis krasID analyzes foundational aspects of KRAS biology using RNA-sequencing and a machine learning algorithm comprising numerous biologic signatures. The classifier predicted preclinical drug response with an accuracy of 0.94 Area Under the Receiver Operator Curve (AUROC) and correctly selected real-world patient responders with an AUROC of 0.80. Kaplan-Meier analysis of the real-world sotorasib patient data considered time on treatment as an available proxy for progression-free survival. This analysis showed that patients classified as "krasID-high" had median time on treatment of almost one year (338 days), compared with those classified as "krasID-low" with median time on treatment of only 158 days (hazard ratio [HR] = 0.35). Taken together, these early results demonstrate that the Genialis krasID classifier can predict response and stratify durable benefit in experimental and clinical settings.

"Genialis krasID is designed to support the entire lifecycle of drug development and clinical care. Because the model incorporates biologies that are intrinsic to KRAS function in the tumor and extrinsic to the surrounding tumor milieu, we expect this biomarker to perform well for diverse drugs across disease settings and mutation status," said Mark Uhlik, Vice President of Biomarker Development at Genialis.

KRAS mutations are prevalent in many common oncologic malignancies, including lung, colorectal, and pancreatic cancers, with frequencies ranging from 25 percent in NSCLC to nearly 95 percent in pancreatic. Even with two FDA approvals of KRAS inhibitors, the rate of patient response (~30-40%) and the durability of responses (~10-11 months) leaves room for improvement. Most biomarkers in the KRAS space measure only KRAS mutation status, which may be necessary to receive the drug but is insufficient to predict or monitor response or to inform further therapeutic interventions. By using high-dimensional gene expression data, Genialis krasID captures underlying biological complexity unique to each individual patient.

"Genialis recognizes an urgent need for patients with lung, colorectal and pancreatic cancers to have access to more informative diagnostic tests that steer them to the best possible medicines for their disease," said Rafael Rosengarten, PhD, CEO of Genialis. "We’re just at the dawn of being able to treat KRAS-driven cancers. With Genialis krasID, we can provide the most complete picture of the diseases we’re trying to defeat, and a plan for how to win."

AACR marks the launch of an early access program (EAP) for Genialis krasID. Over 50 biopharma companies are currently developing more than 70 different KRAS-targeted drugs across over 12 disease indications. The total KRAS therapy market today is estimated at approximately $240 million, with a compound annual growth rate of 36% to reach $10 billion by 2032. Meanwhile, available diagnostics to support KRAS-targeted patient care are limited to mutation-based tests.

Last week, Genialis announced the addition of two new partners as it assembles the world’s most ethnographically diverse cancer data sets. For the new Genialis krasID program, Genialis already has commitments from several marquee partners across biopharma, diagnostics, and clinical research centers and is reserving space to add a handful more of select organizations. Early access program members will gain the opportunity to have their KRAS-related data analyzed by Genialis to establish a foundation for implementing krasID within their translational and clinical workflows. Genialis anticipates a full commercial launch of the biomarker product in September. For more information on Genialis RNA-biomarker programs, please visit View Source

On April 9, 2024 Ferronova reported the initiation of a clinical trial of the company’s FerroTrace nanoparticle technology in patients with gastric and oesophageal cancers (Press release, Ferronova, APR 9, 2024, View Source;Nanoparticle-Trial-Begins-in-Patients-With-Gastric-and-Oesophageal-Cancers [SID1234641961]). It follows the completion of a first-in-human trial in 2020-2022 in oral cancer patients.

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The MAGMAP trial will enrol 60 patients and commenced today with the first patient at the Royal Adelaide Hospital, to be followed by Flinders Medical Centre and Queen Elizabeth Hospital in South Australia, and then expanding to the Peter MacCallum Cancer Centre and Austin Hospital/Olivia Newton John Cancer Centre in Victoria. Trial imaging is supported by the South Australian Health and Medical Research Institute (SAHMRI) and the National Imaging Facility.

The MAGMAP trial (Clinicaltrials.gov ID: NCT05899985) is a multi-centre, partially blinded, side-by-side comparator study to assess the safety and tolerability, feasibility, and potential added diagnostic and clinical value of FerroTrace for mapping high-risk lymph nodes in subjects.

Ferronova Chief Executive Officer Mr Stewart Bartlett said it is potentially an important study offering the promise of an innovative approach for identifying and assessing lymph nodes at high risk of containing cancer.

"Gastric, gastric-oesophageal junction, and oesophageal cancers have very poor outcomes, even where the tumour is localised to a primary location and surrounding lymph nodes where surgery is intended to be curative, and this trial is an important step to test whether our novel technology can improve outcomes in this group of patients."

Studies show following surgery, the 5-year relative survival rates for localised gastric and oesophageal cancers are approximately 74.7% and 48.5% respectively. Where the cancer has also spread to lymph nodes, the 5-year relative survival is only 34.6% and 27.7% [1][2].

Ferronova’s FerroTrace product is a super-paramagnetic iron oxide nanoparticle targeting CD206 receptors found in lymph nodes. It offers a unique targeting mechanism designed to enable a longer lymph node retention time allowing the use of MRI and a handheld surgical magnetic detector to identify and assess lymph nodes containing FerroTrace."

Principal Investigator, Dr Markus Trochsler said the trial will investigate the feasibility of mapping lymph nodes directly draining a primary tumour which theoretically have the highest risk of containing metastasis.

"Gastric and oesophageal cancers are difficult to treat due to unpredictable and extensive lymphatic drainage network in this area of the body, which means lymph nodes containing cancer could potentially be found anywhere from the neck down to the abdomen. At present, when these metastases are very small, they cannot be detected with current imaging technology" Dr Trochsler said.

"This pilot study may lead to providing us with another alternative, being a more informed treatment plan. We are testing whether nanoparticles can identify lymph nodes which are at high-risk of containing cancer cells. It will support us to progress to larger randomised trials where we will investigate tailoring our treatment approach based on the identification and position of these nodes."

Mr Bartlett said the study enrolment is predicted to take 12-15 months, and he hoped the results will lead to new methods of treating patients facing uncertain outcomes.

"The enrolment of the first patient is an important milestone for Ferronova," Mr Bartlett said.

"We are incredibly thankful for the investigators and their support teams, led by Dr Trochsler, as well as Associate Professor Kanhere at the RAH, Professor Watson and Dr Bright at Flinders, Dr Liu at the Austin and Peter Mac, and Dr Dwyer at SAHMRI. They have all put in an incredible amount of work and planning to design and initiate this trial. We look forward to seeing the results when the trial is complete."