On July 23, 2024 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported positive treatment updates from its Phase 2 clinical trial, THIO-101, evaluating THIO sequenced with the immune checkpoint inhibitor (CPI) cemiplimab (Libtayo) in patients with advanced non-small cell lung cancer (NSCLC) who failed two or more standard-of-care therapy regimens (Press release, MAIA Biotechnology, JUL 23, 2024, View Source [SID1234645029]).

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The trial’s therapeutic regimen is cycled every 3 weeks, with THIO 180mg administered in 60mg incremental doses on days 1, 2 and 3, followed by immune activation on day 4 (no dosing), and cemiplimab 350mg administered on day 5. As of the latest clinical cutoff date, June 12, 2024:

6 patients remain on treatment following at least 12 months of therapy.
Treatment with THIO followed by cemiplimab has been well tolerated throughout the trial, with much lower toxicity compared to standard-of care treatments.
Continuing treatment past 12 months demonstrates safety, efficacy and ongoing benefit from MAIA’s novel telomere targeting NSCLC therapy.
"Our longest treated patient so far has completed 21 cycles of THIO sequenced with a CPI, and 6 patients who have crossed the 12-month survival follow-up are continuing the treatment," said Vlad Vitoc, M.D., Chairman and Chief Executive Officer of MAIA. "With current therapies, second-line patients’ treatment duration is usually around 3-4 months1 and third-line is even lower than that. It is very encouraging to see that our patients can remain on treatment for much longer. The ongoing benefits of THIO in longer-term patients are particularly notable, signifying THIO’s potential as a durable and efficacious treatment for advanced NSCLC patients faced with limited options."

https://www.sciencedirect.com/science/article/pii/S0169500217304373

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.

About THIO-101, a Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to cemiplimab (Libtayo) will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. Treatment with cemiplimab (Libtayo) followed by THIO has been generally well-tolerated to date in a heavily pre-treated population. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

On July 23, 2024 Blue Earth Therapeutics, a Bracco company and emerging leader in the development of innovative next generation therapeutic radiopharmaceuticals, reported the signing of a clinical research collaboration with University College London (UCL) (Press release, Blue Earth Therapeutics, JUL 23, 2024, View Source [SID1234645028]). The collaboration is centered on a Phase 1/2 trial designed to evaluate the safety, tolerability, radiation dosimetry and anti-tumour activity of the company’s 225Ac-rhPSMA-10.1 in men with metastatic castrate-resistant prostate cancer who have previously responded to lutetium 177 (177Lu)-PSMA therapy. The work will be conducted at the UCL Cancer Institute in London, UK, by the Treatment Resistance Group under the leadership of Professor Gerhardt Attard, MD PhD FRCP. Professor Attard is the John Black Charitable Foundation Endowed Chair in Urological Cancer Research, and is a highly regarded prostate cancer clinical trialist.

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225Ac-rhPSMA-10.1 is the second compound in Blue Earth Therapeutics’ investigational pipeline. It is based on innovative radiohybrid PSMA technology, which allows for development of therapeutic radiopharmaceuticals that may be labelled with either beta- or alpha-emitting isotopes. The pharmacokinetic profile of rhPSMA-10.1 was carefully optimised during development to maximise the retention of radioactivity in tumour deposits whilst sparing normal tissue as far as possible. Pairing these properties with longer lived isotopes like 225Ac may allow the delivery of very high radiation doses to the cancer cells. Blue Earth Therapeutics has an ongoing clinical trial underway that uses the beta-emitting radioisotope lutetium 177 (177Lu) to radiolabel rhPSMA-10.1, and is building on that work by now radiolabelling the compound with the alpha-emitting radioisotope 225Ac.

"Our goal at Blue Earth Therapeutics is to deliver precise, targeted therapy specific to a patient’s condition," said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Therapeutics. "This collaboration aims to rapidly translate alpha-labelled rhPSMA-10.1 from the laboratory to the clinic, with the hope to help patients who have advanced prostate cancer. We are delighted to collaborate with an illustrious academic institution such as UCL which is regularly ranked in the top 10 academic institutions globally, and look forward to working with Professor Attard and his group on this important UK clinical research initiative."

"We are pleased to enter into this broad research collaboration with UK-based Blue Earth Therapeutics, as both of our institutions share a vision to improve cancer treatment for patients," said Professor Attard, MD PhD FRCP. "Despite the development of several new therapeutic options for castration resistant prostate cancer in the last 20 years, treatment resistance is common and leads to thousands of premature deaths annually in the UK. Precision-delivered radiation therapy using radioligands provides an opportunity for selectively targeting resistant prostate cancer. We believe that delivery of radiation by means of alpha particles is a very promising area of research and we look forward to starting clinical testing of rhPSMA-10.1 for patients with aggressive, treatment-resistant prostate cancer."

About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) compounds consist of a radiohybrid ("rh") Prostate-Specific Membrane Antigen-targeted receptor ligand, which is internalised by prostate cancer cells, which can be radiolabelled with imaging isotopes for PET imaging, or with therapeutic isotopes for therapeutic use – providing the potential for creating a true theranostic technology. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Therapeutics and Blue Earth Diagnostics work closely on the development of 177Lu‐rhPSMA‐10.1 and 225Ac-rhPSMA-10.1. rhPSMA compounds for therapeutic use are investigational agents and have not received regulatory approval.

On July 23, 2024 AffyImmune, a clinical-stage biotechnology company committed to developing novel, first-in-class chimeric antigen receptor (CAR) T cell therapies, reported the designation of Regenerative Medicine Advanced Therapy (RMAT) by the U.S. Food and Drug Administration (FDA) for its CAR T-cell product candidate, AIC100 as a potential treatment for patients with recurrent anaplastic thyroid cancer (ATC), the most aggressive form of the disease (Press release, AffyImmune Therapeutics, JUL 23, 2024, View Source [SID1234645027]).

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"We believe this important recognition from the FDA further supports the therapeutic potential of AIC100 to change the current treatment paradigm in advanced thyroid cancer and potentially other forms of aggressive solid tumors," said Daniel Janse, Ph.D., CEO at AffyImmune. "RMAT designation was granted following the FDA’s review of safety and efficacy data from the first ten patients dosed with AIC100 in our Phase 1 study. We believe the RMAT designation reinforces the potential ability of AIC100 to meet the high unmet medical need in recurrent ATC, an aggressive disease where a standard of care is currently not available."

RMAT designation was designed to expedite the development and review of regenerative medicine therapies. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious condition, and preliminary clinical evidence indicates the therapy has the potential to address unmet medical needs for the disease. Sponsor companies receiving RMAT designation can benefit from increased interactions with the FDA involving senior managers, with the goal of expediting drug development.

"We remain focused on advancing the development of AIC100 for patients and families living with this devastating cancer," said Sonal Gupta, M.D., Ph.D., Senior Vice President and Head of Clinical Development. "Receiving RMAT designation helps facilitate this goal by enabling increased dialogue with the FDA to expedite our development plan for our affinity-tuned CAR T therapy. We look forward to working closely with the FDA and other regulatory agencies as we continue to advance this program."

At ASCO (Free ASCO Whitepaper) 2024, AffyImmune reported interim results from their Phase 1 study evaluating the safety and efficacy of AIC100, an ICAM-1 targeting and affinity-tuned LFA-1 binder CAR T-cell therapy, in patients with advanced thyroid cancer. Notably, a metabolic complete response was achieved in one patient with ATC, the most aggressive form of the disease.

For more information about the Phase 1 study, visit www.clinicaltrials.gov (NCT04420754).

On July 23, 2024 Triastek Inc. ("Triastek"), a global leader in 3D printing pharmaceuticals, reported that it has entered into a research collaboration and platform technology license agreement with BioNTech SE ("BioNTech"), a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases (Press release, BioNTech, JUL 23, 2024, View Source [SID1234645026]). Under the agreement, the companies will develop RNA therapeutics for oral delivery based on 3D printing technology. The collaboration aims to provide groundbreaking therapies to address unmet medical needs in an easy to administer oral formulation.

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Triastek will contribute to the collaboration its expertise in innovative oral tablet designs made possible by 3D printing aimed at optimizing delivery of RNA therapeutics across the gastrointestinal mucosa, minimizing degradation in the gastrointestinal tract, and delivering RNA therapeutics to the portion of the gastrointestinal tract where absorption will potentially be the greatest. Triastek’s ability to create tablet structures with unique external and internal tablet geometries, including multiple-layer and multi-compartment designs, will be leveraged, aiming to optimize delivery of novel RNA therapeutics.

"We are immensely honored to announce our collaboration with BioNTech, a leader in revolutionizing patient care with transformative medicines," stated Dr. Senping Cheng, Founder, and CEO of Triastek. "We believe this collaboration stands as a promising milestone in advancing oral RNA therapeutics using 3D printing technology and aims to set new benchmarks in the development of large molecule oral drugs. We are committed to working diligently together to make breakthroughs in oral delivery of RNA therapeutics."

Under the terms of the agreement, Triastek will receive an upfront payment of $10 million, and will be eligible to receive development, regulatory and commercial milestone payments potentially totaling over $1.2 billion as well as tiered royalties on potential future product sales.

On July 23, 2024 Nuvation Bio Inc. (NYSE: NUVB), a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported multiple updates for its taletrectinib program (Press release, Nuvation Bio, JUL 23, 2024, View Source [SID1234645025]). Data from the global, pivotal Phase 2 TRUST-II study has been accepted for an oral presentation at WCLC 2024 taking place September 7-10 in San Diego, California. Pooled data from both pivotal Phase 2 studies, TRUST-I and TRUST-II, has been accepted for a poster presentation at ESMO (Free ESMO Whitepaper) 2024 taking place September 13-17, in Barcelona, Spain. The pooled data presented at ESMO (Free ESMO Whitepaper) will support the Company’s NDA in the United States. Additionally, the U.S. FDA has granted Orphan Drug Designation to taletrectinib for the treatment of multiple NSCLC indications, including ROS1-positive NSCLC.

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"We are excited to share these program updates as we continue toward our goal of bringing taletrectinib to patients with ROS1-positive NSCLC. We look forward to sharing the latest TRUST-II data at WCLC 2024 and pooled TRUST-I and TRUST-II data at ESMO (Free ESMO Whitepaper) 2024. The pooled data to be presented at ESMO (Free ESMO Whitepaper) will support our NDA in the U.S. and, we believe, position us to commercialize taletrectinib in 2025," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "Further, we are pleased with the FDA’s recent determination that taletrectinib qualifies for Orphan Drug Designation, which represents another key regulatory milestone for this important program."

Taletrectinib was granted Orphan Drug Designation for the treatment of ROS1- positive, NTRK-positive, ALK-positive, LTK-positive, ACK1-positive, or DDR1-positive NSCLC. The FDA’s Office of Orphan Drug Products grants this designation to support drug candidates in development for underserved patient populations or rare disorders that affect fewer than 200,000 people in the United States. Orphan Drug Designation qualifies a candidate for various development incentives, including tax credits for eligible clinical trials, waiver of application fees and potential market exclusivity for seven years upon FDA approval.

Taletrectinib is being evaluated for the treatment of patients with ROS1-positive NSCLC in two pivotal Phase 2 studies, TRUST-I (NCT04395677) in China and TRUST-II (NCT04919811), a global pivotal study.

WCLC Presentation Overview:

Title: Efficacy and Safety of Taletrectinib in Patients with ROS1+ Non–Small Cell Lung Cancer: The Global TRUST-II Study
Presenter: Geoffrey Liu, MD
Date: September 10, 2024
Session Time: 11:15 a.m. – 12:30 p.m. PDT
Session: MA06 – New Strategies in ALK, ROS1, NTRK, BRAF, and MET NSCLC
Abstract: 1752

ESMO Presentation Overview:

Title: Pooled Efficacy and Safety From 2 Pivotal Phase 2 Trials of Taletrectinib in Patients (Pts) With Advanced or Metastatic ROS1+ Non–Small Cell Lung Cancer (NSCLC)
Presenter: Maurice Perol, M.D.
Date: September 14, 2024
Session Time: Poster Lunch, 12:00-1:00 p.m. CEST (on display from 9:00 a.m. – 5:00 p.m. CEST)
Session: Poster Display, NSCLC, Metastatic
Abstract: 1289P

The materials will be made available on the Publications section of nuvationbio.com the day of the respective presentations.

About Taletrectinib

Taletrectinib is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with advanced ROS1-positive NSCLC. Taletrectinib is being evaluated for the treatment of patients with advanced ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study. Taletrectinib has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with ROS1-positive NSCLC and Breakthrough Therapy Designations by both the U.S. FDA and China’s National Medical Products Administration (NMPA) for the treatment of patients with advanced or metastatic ROS1-positive NSCLC. Based on results of the TRUST-I clinical study, China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who either have or have not previously been treated with ROS1 tyrosine kinase inhibitors (TKIs).

About ROS1-positive NSCLC

More than one million people globally are diagnosed with NSCLC annually, the most common form of lung cancer. It is estimated that approximately 1-3% of people with NSCLC are ROS1-positive. Up to 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain, increasing up to 55% for those whose cancer has progressed following initial treatment. While people with other types of lung cancer have seen great advances, there has been limited progress for people with ROS1-positive NSCLC who remain in need of new options.