On February 5, 2024 Triumvira Immunologics, a clinical-stage company developing novel, targeted autologous and allogeneic T cell therapeutics that co-opt the natural biology of T cells to treat patients with solid tumors, reported that the first patient has been dosed in its TACTIC-3 trial, a Phase I/II study, (NCT05862324) investigating the safety and efficacy of autologous TAC-T cell asset, TAC101-CLDN18.2, targeting Claudin 18.2+ solid tumors (Press release, Triumvira Immunologics, FEB 5, 2024, View Source [SID1234639846]). TAC101-CLDN18.2 is a novel cell therapy based on genetically engineered autologous T cells expressing a T-cell Antigen Coupler (TAC) that harnesses the inherent signaling pathways of the native T cell receptor complex and targets Claudin 18.2, an epithelial transmembrane protein overexpressed in gastric cancer and several other solid tumor types.

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"Claudin 18.2 is a promising target for cell therapy," said Andreas Bader, Ph.D., Chief Scientific Officer of Triumvira Immunologics. "Among normal tissues, it is restricted to the stomach and hidden between neighboring cells. In gastric cancer and a few other solid tumors, however, it is accessible and abundantly expressed on tumor cell surfaces and, therefore, it represents a significant tumor selective opportunity to address these types of cancers."

"We are delighted to initiate this study at such a pivotal moment for Triumvira as we advance an exciting clinical program aimed at addressing a substantial therapeutic gap for solid tumors," said Deyaa Adib, M.D., Chief Medical Officer of Triumvira Immunologics. "TAC101-CLDN18.2 represents a unique new therapy in our pipeline that has the potential to provide a new therapeutic solution for CLDN18.2 positive solid tumors including gastric, lung, ovarian and pancreatic cancers. There are currently no other approved treatment options against CLDN18.2, and novel therapeutics in development, such as TAC101-CLDN18.2, offer hope to a patient segment that constitutes ~40% of the gastric cancer population in the U.S. alone. Through our TAC technology, which harnesses the inherent signaling pathways of native TCRs, we aspire to bring forward innovative, chemotherapy-sparing therapeutic strategies for solid tumors."

TACTIC-3 is a first-in-human study investigating TAC101-CLDN18.2 to evaluate the safety, recommended Phase II dose (RP2D), pharmacokinetic profile, and efficacy in subjects with CLDN18.2+ solid tumors who have been treated with at least 2 lines of prior therapy in Phase I and between 2-4 lines of prior therapy in Phase II. In each phase, subjects with pancreatic ductal adenocarcinoma may have been treated with 1 line of prior antineoplastic therapy. In addition, subjects who are being treated with the current lines of therapy with no demonstrated benefit may also be eligible on the condition that no measurable disease was reported at baseline as a starting reference point.

On February 5, 2024 Papyrus Therapeutics Inc., a biotechnology platform company for the development of potent, multi-cancer, tumor suppressor precision therapies for solid cancers, reported the upcoming poster presentation entitled "Oncolytic Vaccinia Virus Carrying OPCML Tumor Suppressor is active in Epithelial Ovarian Cancer" has been accepted for presentation at the forthcoming AACR (Free AACR Whitepaper) meeting in San Diego in the Immunology category from 9.00am – 12.30pm PT on April 10th (View Source) (Press release, Papyrus Therapeutics, FEB 5, 2024, View Source;utm_medium=rss&utm_campaign=papyrus-therapeutics-to-present-at-aacr-april-5-10-san-diego [SID1234639845]).

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The data demonstrate that vaccinia virus directed OPCML protein expression enhances OVV selectivity against ovarian cancer cells through direct oncolysis, inhibition of specific RTKs, suppression of angiogenesis, and activation of antitumor immune responses synergistically when combined with an anti-PD-1 inhibitor.

According to Papyrus’ co-founder / chief scientific officer, and renowned translational medical oncologist Hani Gabra, PhD FRCP, "A short treatment with novel OVV-OPCML / anti-PD-1 inhibitor combination showed a 50% increase in median survival in the mice studied, an encouraging outcome demonstrating promise as a targeted strategy for ovarian cancer treatment. This is important given the relatively poor treatment results with check-point inhibitors to date in ovarian cancer."

On February 5, 2024 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported that findings from Patient-Reported Outcomes (PROs) of participants in the phase 2/3 QUILT 3.032 study of N-803 plus BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) were published by the peer-reviewed journal Urology Practice (Press release, ImmunityBio, FEB 5, 2024, View Source [SID1234639844]). These PROs support the positive interim results from the study published in NEJM Evidence, wherein 71% of patients in cohort A with CIS with or without Ta/T1 disease achieved a complete response.

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The published PROs based on a May 16, 2022 data cutoff indicate that both physical function and global health as self-reported by QUILT 3.032 participants with BCG-unresponsive NMIBC CIS (cohort A) or papillary disease (cohort B), remained stable over the 2-year course of the study for patients who completed the PRO questionnaires and reached 24 months on-study. In addition, overall both cohort A and B participants who reached month 24 on-study and also completed an NMIBC-specific questionnaire focusing on the challenges of bladder cancer, also reported no decline of their health or urinary tract-related symptoms while in the study. Overall, participants who achieved a complete response with the novel combination therapy reported better physical function by month six of the study than those who did not achieve a complete response.

"The self-reported stability of health and physical function over the course of the study by the participants reflect another aspect of safety and tolerability of this new combination therapy," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "Taken together with the positive response rate in cohort A of over 70%, the persistence of responses and cystectomy avoidance, these QoL findings suggest a favorable risk-benefit ratio for this potential new therapeutic option for patients with BCG-unresponsive bladder cancer."

The finding of relative stability of global health and physical function during the course of the study is similar to that reported by others for BCG monotherapy, suggesting the novel combination is as tolerable as treatment with BCG alone.

"Many current therapies for bladder cancer slow disease progression but can cause debilitating side effects," said Principal Investigator Karim Chamie, M.D., Associate Professor of Urology at UCLA. "The data from the QUILT 3.032 Quality of Life study suggest that many patients not only have a durable response but also report no decline in physical function, which is very important for these patients."

QUILT 3.032 Study Details

The ongoing phase 2/3 open-label multicenter registrational study QUILT 3.032 (NCT03022825) is evaluating the safety and efficacy of the investigational interleukin-15 superagonist N-803 (also known as Anktiva and nogapendekin alfa inbakicept, NAI) in combination with a standard therapy for NMIBC, bacillus Calmette-Guerin (BCG), in patients who failed or in whom cancer returned after BCG monotherapy, and thus were diagnosed as BCG-unresponsive. The study comprises three cohorts, with cohort A enrolling patients with carcinoma in situ (CIS) with or without Ta/T1 disease and cohort B enrolling patients with high grade Ta/T1 papillary disease. Both cohorts A and B received combination N-803 plus BCG therapy. Cohort C patients, with CIS +/- Ta/T1 disease received N-803 monotherapy.

The primary end point is the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B.
Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival are secondary end points for cohort A.
Cohort C was discontinued due to a low response rate with N-803 monotherapy, per study design.
The FDA has accepted for review ImmunityBio’s resubmission of its biologics license application (BLA) for N-803 plus BCG for the treatment of BCG-unresponsive NMIBC CIS with or without Ta or T1 disease, and has set a user fee goal date (PDUFA date) of April 23, 2024.
Bladder cancer is the 10th most-commonly diagnosed cancer, with approximately 80% of newly diagnosed cases being NMIBC. Intravesical (directly to the bladder) instillation of BCG after removal of cancer tissue from the lining of the bladder (transurethral resection of the bladder tumor; TURBT) is Standard-of-Care (SoC) for intermediate and high-risk NMIBC patients, but up to 40% of patients will fail BCG therapy and ~50% will relapse after an initial response and given a diagnosis of being BCG-unresponsive. Therapies approved by the FDA for this indication include pembrolizumab, nadofaragene, combined gemcitabine and docetaxel, and valrubicin. Radical cystectomy – surgical removal of the bladder – is also an option for these patients. QUILT 3.032 is being conducted to address the need for a safe, effective therapeutic option for BCG-unresponsive NMIBC patients that provides an opportunity for avoidance of radical cystectomy.

N-803 is investigational. Safety and efficacy have not been established by any Health Authority or Agency, including the FDA.

On February 5, 2024 Immix Biopharma, Inc. (Nasdaq: IMMX) (the "Company"), a clinical-stage biopharmaceutical company trailblazing cell therapies in autoimmune disease, reported that it intends to offer and sell shares of its common stock in an underwritten public offering (Press release, Immix Biopharma, FEB 5, 2024, View Source [SID1234639843]). All of the shares of common stock in the underwritten public offering are to be sold by the Company. The Company also expects to grant the underwriters a 30-day option to purchase additional shares of common stock offered in the public offering. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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The Company intends to use the net proceeds from the proposed offering for NXC-201 clinical trials, working capital and general corporate purposes.

Titan Partners Group, LLC, a division of American Capital Partners, LLC, is acting as sole book-running manager for the offering.

A shelf registration statement relating to the shares of common stock to be issued in the proposed offering was filed with the Securities and Exchange Commission ("SEC") and declared effective by the SEC. A preliminary prospectus supplement relating to the proposed offering has been filed with the SEC and is available on the SEC’s website at View Source A final prospectus supplement describing the terms of the proposed offering will be filed with the SEC. The offering will be made only by means of the preliminary prospectus supplement and the accompanying base prospectus, as may be further supplemented by any free writing prospectus and/or pricing supplement that the Company may file with the SEC. Copies of the preliminary prospectus supplement and accompanying base prospectus relating to the offering may be obtained from Titan Partners Group, LLC, a division of American Capital Partners, LLC, 4 World Trade Center, 29th Floor, New York, NY 10007, by email at [email protected], or by calling (929) 833-1246.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On February 5, 2024 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that in January 2024, the first patient was enrolled and dosed in the Phase 2a expansion portion of the Company’s Acclaim-1 clinical study of Reqorsa Therapy (quaratusugene ozeplasmid) in combination with AstraZeneca’s Tagrisso to treat patients with late-stage non-small cell lung cancer (NSCLC) (Press release, Genprex, FEB 5, 2024, View Source [SID1234639842]).

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"We are encouraged by the very promising Phase 1 results in the Acclaim-1 trial, which demonstrated the combination of REQORSA and Tagrisso was well tolerated at all three dose levels with evidence of efficacy observed in patients with non-small cell lung cancer (NSCLC) whose disease has progressed on Tagrisso," stated Mark Berger, Chief Medical Officer of Genprex. "We are excited to begin the Phase 2a expansion portion of Acclaim-1, which will examine the toxicity profiles of different cohorts as well as efficacy and other clinical endpoints."

Data from the Phase 1 dose escalation portion of the Acclaim-1 study were presented at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC International Conference for Molecular Targets and Cancer Therapeutics Meeting in October 2023. The data reported results from twelve patients with advanced, epidermal growth factor receptor (EGFR) mutant NSCLC whose disease progressed after Tagrisso treatment. REQORSA was generally well tolerated, as there were no dose limiting toxicities.

While the Phase 1 portion of the clinical trial was designed primarily to assess safety, promising efficacy results were also observed. One patient at the 0.06 mg/kg dose level, previously treated with carboplatin, pemetrexed, and Tagrisso, had a partial remission (PR) by investigator evaluation and treatment is now ongoing in the trial after 28 cycles, which is approximately 19.5 months. Another patient who is at the 0.09 mg/kg dose level, previously treated with Tagrisso, had stable disease and treatment was ongoing after 14 cycles, or approximately 10 months. And a third patient previously treated with cisplatin, pemetrexed, carboplatin, and Tagrisso at the 0.12 mg/kg dose level has stable disease and is continuing to receive REQORSA after 14 cycles, or approximately 10 months. The extended progression free survival (PFS) of each of these patients is consistent with long-term PFS seen in several patients in prior early stage clinical trials of REQORSA, and is not expected with treatment with Tagrisso alone after progression on Tagrisso1. PFS is the primary endpoint of both the Phase 2a expansion portion and the Phase 2b randomized portion of the Acclaim-1 study.

"Advancing Acclaim-1 marks an important milestone for Genprex. We are proud of the progress we have made thus far and are encouraged by REQORSA’s potential to improve outcomes for patients battling NSCLC. We look forward to an interim analysis from the Phase 2a study in 2025 and expect those results will further validate our novel gene therapy approach to treating lung cancer patients," said Rodney Varner, President, Chairman and Chief Executive Officer at Genprex.

REQORSA, the Company’s lead product candidate, is being evaluated in three clinical trials as a treatment for NSCLC and small cell lung cancer (SCLC). Each of the three lung cancer clinical programs has received a Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the treatment of that patient population, and the SCLC program has also received an FDA Orphan Drug Designation.

About Acclaim-1 Clinical Trial

The Acclaim-1 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA, in combination with Tagrisso in patients with late-stage NSCLC with activating epidermal growth factor receptor ("EGFR") mutations whose disease progressed after treatment with Tagrisso.

The Phase 1 dose escalation portion of the Acclaim-1 trial has been completed. The Phase 2a expansion portion of the study is expected to enroll approximately 66 patients, half of whom will have received only Tagrisso treatment and the other half will have received Tagrisso treatment and chemotherapy, to determine toxicity profiles of patients with different eligibility criteria, as well as efficacy and other endpoints. There will be an interim analysis following the treatment of 19 patients in each cohort. The Phase 2b randomized portion of the study is expected to enroll approximately 74 patients to be randomized 1:1 to receive either REQORSA and Tagrisso combination therapy or platinum-based chemotherapy. The primary endpoint of the Phase 2b portion of the trial is progression-free survival, which is defined as time from randomization to progression or death. An interim analysis will be performed at 28 events.

About Reqorsa Therapy
REQORSA (quaratusugene ozeplasmid) for NSCLC and SCLC consists of the TUSC2 gene expressing plasmid encapsulated in non-viral nanoparticles made from lipid molecules (Genprex’s ONCOPREX Nanoparticle Delivery System) with a positive electrical charge. REQORSA is injected intravenously and specifically targets cancer cells, which generally have a negative electrical charge. REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing their uptake by normal tissue. REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, and modulates the immune response against cancer cells.

Genprex’s strategy is to develop REQORSA in combination with currently approved therapies and believes that REQORSA’s unique attributes position it to provide treatments that improve on these current therapies for patients with NSCLC, SCLC, and possibly other cancers.

Tagrisso is a registered trademark of AstraZeneca plc.