1stOncology™: Cancer Intelligence Service – Page 60 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Two Additional Complete Responses and Three Partial Responses in azer-cel CAR T Phase 1b trial

On July 14, 2025 Imugene Limited (ASX: IMU), a clinical-stage immuno-oncology company, reported exciting new data from its Phase 1b clinical trial evaluating azer-cel (azercabtagene zapreleucel) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Imugene, JUL 14, 2025, https://mcusercontent.com/e38c43331936a9627acb6427c/files/9dcc6e8a-a173-fb47-bc66-6b21c92ab09f/Two_Additional_Complete_Responses_in_azer_cel_Ph1b_trial.pdf [SID1234654361]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

In February 2025, Imugene announced that a total of four out of seven patients had achieved a Complete Response (CR), defined as the disappearance of all signs of cancer in response to treatment. Since then, two additional patients have also achieved a Complete Response, and three patients have achieved Partial Response (cancer reduction by at least 50%) bringing the best overall response rate to 75% and the CR rate to 55%. The duration of response continues to mature. These patients are being treated with azer-cel and interleukin 2 (IL -2).

Evaluable
patients

Treatment

Overall Response Rate (ORR)

Complete Response (CR)

At Day 60

Best Durability (Time of response)

DLBCL

Lymphodepletion (LD)1 +azer-cel

+Interleukin-2 (IL-2)

9/12 (75%)

6/11 (55%)

>450 days on going

For approved, autologous CD19 CART products, the average time to best response is 2-3 months with some patients taking up to 6 months to achieve their best response.

Azer-cel is being developed as a potential allogeneic, off-the-shelf, CAR T-cell therapy, addressing key limitations of approved autologous CAR T drugs, including geographical access to treatment centres, manufacturing complexity and time to receive treatment (on-demand).

Based on the updated response rate and maturing durability data, as well as having been awarded FDA Fast Track Designation for DLBCL in March 2025, Imugene will request a Type B (End of Phase 1) Meeting in Q4 2025, with the US FDA to present the data and to discuss designs for a pivotal / registrational trial for azer-cel.

Leslie Chong, Managing Director and CEO of Imugene, said:

"We are very pleased with the continued positive data coming from the azer-cel trial, which further reinforces its potential as a treatment for DLBCL patients who have failed several previous lines of therapy. The data also significantly improves our position from both a regulatory and commercial standpoint, and we look forward to expanding on these discussions with the FDA.

Additionally, given the positive results, we are opening the trial to other niche blood cancer indications, such as PCNSL and other subtypes of B Cell Lymphoma, for CAR T naïve patients. This is a high unmet need with potential to expedite and expand the scope of azer-cel."

Dr John Byon, Chief Medical Officer of Imugene, said:

"DLBCL remains one of the most aggressive forms of lymphoma, and despite the existing therapies, there are a large number of patients that still face relapse or resistance. We are seeing significant potential from azer-cel to date in its ability to provide a critical step forward for these patients who have relapsed on multiple therapies, offering deep and durable responses with a one-time treatment.

We remain deeply committed to transforming the standard of care in difficult-to-treat blood cancers, where significant unmet medical need still exists."

The FDA Fast Track Designation for DLBCL received for azer-cel is designed to facilitate the development and expedite the review of drugs that address serious or life-threatening conditions and meet an unmet medical need. Benefits of the designation include more frequent meetings with the FDA to discuss development plans, the option for rolling review of regulatory submissions, and potential eligibility for Accelerated Approval and Priority Review upon meeting relevant criteria.

Imugene continues to actively enrol patients into the Phase 1b azer-cel trial at ten US sites with up to six sites in Australia planned, after the first Australian patient was dosed in January 2025 at Royal Prince Alfred Hospital in Sydney, resulting in a Complete Response.

About the Phase 1b azer-cel trial

The azer-cel allogeneic CAR T trial is an ongoing, open-label, multi-centre Phase 1b clinical trial in the U.S. and Australia, for CAR T relapsed patients with DLBCL. The study has recently expanded to include and treat CAR T naïve patients diagnosed with a broad range of Non-Hodgkins lymphomas including primary central nervous system lymphoma (PCNSL), chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), Waldenstrom macroglobulinemia (WM) and follicular lymphoma (FL). Treatment with azer-cel, lymphodepletion (LD) and IL-2 is showing promising results with evidence of meaningful clinical activity, and durability of response. Additionally, the safety profile is manageable and generally well tolerated.

About diffuse large B cell lymphoma (DLBCL)

DLBCL is an aggressive and fast-growing type of non-Hodgkin’s lymphoma (NHL), a type of blood cancer. DLBCL is the most common type of NHL, with approximately 160,000[1] global cases per year and approximately 30,000 new cases per year in the U.S. Relapsed/refractory DLBCL has a high unmet medical need; ~60% of patients treated with approved autologous CD19 CAR T relapse.

About primary central nervous system lymphoma (PCNSL)

PCNSL is a rare and aggressive form of non-Hodgkin lymphoma (NHL), a type of blood cancer that originates in the brain, spinal cord, leptomeninges, or eyes, usually without evidence of systemic disease. In the U.S., there are approximately 1,500 to 1,800 new cases per year with limited approved treatment options and is a high unmet need. Currently, there are no CAR T-cell products approved for the treatment of PCNSL providing a unique opportunity for azer-cel to treat CART naïve patients.

About other types of B Cell Lymphoma

Other subtypes of non-Hodgkin lymphoma (NHL) include chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), the most common slow growing leukemia that can become resistant to therapy; marginal zone lymphoma (MZL), a slow-growing B-cell lymphoma that arises in lymphoid tissues associated with mucosal sites like the stomach and lung; Waldenström macroglobulinemia (WM), a rare slow-growing lymphoma characterized by excess IgM production, which can cause multiple complications ; and follicular lymphoma (FL), a common slow-growing NHL that can become more aggressive. While several targeted therapies and monoclonal antibodies are available for these types of B Cell Lymphoma, relapsed or refractory disease remains an ongoing challenge, highlighting the ongoing need for continued innovation and new and better treatments.

About Interleukin 2 (IL-2)

IL-2 is a cytokine (a protein that affects what happens between cells in the immune system) that helps T-cells (which are part of the immune system that help fight cancer) grow and survive. IL-2 has been shown to help T cells live longer and to enhance the cancer killing functions of CAR T cells, making them more effective at targeting and killing cancer cells.

CARsgen Successfully Defends Its GPC3 CAR-T Patent at the EPO

On July 13, 2025 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on developing innovative CAR T-cell therapies, reported a favorable outcome in opposition proceedings before the European Patent Office (EPO) concerning its European patent EP3445407, which covers its GPC3-targeted CAR-T cell therapy (Press release, Carsgen Therapeutics, JUL 13, 2025, View Source [SID1234654362]).

On July 3, 2025, a U.S.-based biotechnology — the sole appellant among the original two opponents — formally withdrew its appeal against the EPO Opposition Division’s earlier decision to maintain the patent. This withdrawal renders the EPO’s decision final and binding for the opponents, effectively concluding their part in the opposition process.

The patent was granted by the EPO in 2022 and opposed by two parties in 2023. Following oral proceedings, the EPO Opposition Division issued a decision to maintain the patent in amended form, upholding key claims related to the use of GPC3 CAR-T cell therapy following cyclophosphamide and fludarabine lymphodepletion pretreatment, in the treatment of liver cancer, lung cancer, ovarian cancer, breast cancer, gastric cancer, and thyroid cancer. Following the decision, only one opponent filed an appeal within the allowable period. That appeal has now been withdrawn.

Under EPO procedures, the opponents or any other third party can no longer challenge the patent at the EPO. This development further reinforces CARsgen’s intellectual property position in the field of GPC3-targeted CAR-T therapies, a promising and innovative approach for the treatment of solid tumors.

Milestone Pharmaceuticals Announces Proposed Public Offering

On July 11, 2025 Milestone Pharmaceuticals Inc. ("Milestone") (Nasdaq: MIST) reported that it has commenced an underwritten public offering (the "Offering") of its common shares, accompanying Series A warrants to purchase common shares (the "Series A Warrants") and accompanying Series B warrants to purchase common shares (the "Series B Warrants"), and, in lieu of common shares to certain investors that so choose, pre-funded warrants to purchase common shares, accompanying Series A Warrants and accompanying Series B warrants (Press release, Milestone Pharmaceuticals, JUL 11, 2025, View Source [SID1234654369]). All securities to be sold in the Offering will be sold by Milestone. The Offering is subject to market and other 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.

Milestone intends to use the net proceeds from the Offering, together with existing cash and cash equivalents, to fund the clinical development and commercial launch of etripamil in its lead indication of paroxysmal supraventricular tachycardia (PSVT), as well as for working capital and other general corporate purposes.

TD Cowen, Piper Sandler & Co. and Wells Fargo Securities are acting as joint book-running managers for the Offering. H.C. Wainwright & Co. is acting as lead manager for the Offering.

The securities described above are being offered by Milestone pursuant to a shelf registration statement on Form S-3 (File No. 333-283162), including a base prospectus, that was declared effective by the U.S. Securities and Exchange Commission (the "SEC") on November 22, 2024. The Offering is being made only by means of a prospectus supplement and accompanying prospectus that form a part of the registration statement. A preliminary prospectus supplement related to the Offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. A copy of the preliminary prospectus supplement and the accompanying prospectus relating to the Offering may also be obtained, when available, from: TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, NY 10017, by telephone at 855-495-9846, or by email at [email protected]; Piper Sandler, Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, or by telephone at (800) 747-3924, or by email at [email protected]; and Wells Fargo Securities, LLC, 90 South 7th Street, 5th Floor, Minneapolis, MN 55402, or by telephone at 800-645-3751 (option #5), or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities described herein, 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.

Elegen and Nutcracker Therapeutics to Pilot First Fully Cell-Free Manufacturing Process for RNA-based Personalized Cancer Therapeutics

On July 11, 2025 Elegen, a global leader in next-generation DNA manufacturing, and Nutcracker Therapeutics, a global leader in next-generation RNA design and manufacturing, reported the launch of a pilot program to demonstrate the industry’s first fully synthetic, cell-free manufacturing platform for RNA-based personalized cancer therapeutics (PCTs). The pilot marks another step toward making PCTs more accessible, timely, and scalable (Press release, Nutcracker Therapeutics, JUL 11, 2025, View Source [SID1234654354]).

As late-stage PCT clinical trials progress and therapy developers work to create the next generation of PCTs, the speed, reliability, scaling and cost of traditional production methods pose a major challenge. Specifically, the first step of DNA template production is hindered by the use of bacterial cells in the process, which can be unreliable and introduce contamination that must be removed. The second step of GMP-grade RNA production from the template is impeded by a slow, unreliable, and inefficient process in which only one therapy can be made per GMP suite. Consequently, PCT production is slow, very costly, and does not scale for individualized therapies — a new manufacturing paradigm is needed.

Nutcracker Therapeutic’s NMU-Symphony system, the second generation of its Nutcracker Manufacturing Unit (NMU), brings the fastest, most scalable, and cost-efficient GMP RNA manufacturing platform available today. Fully enclosed and built for speed, it reliably delivers clinical-grade PCTs consistent with just a three-week overall turnaround time, from RNA sequence design to released nanoparticle formulated drug product — cutting traditional timelines in half. By incorporating Elegen’s cell-free GMP-ready DNA template production, the combination of the two platforms will enable an even faster and more scalable synthesis of longer, more complex neo-antigen sequences, while eliminating risks of bioburden and endotoxin contamination.

With a faster, more reliable and lower-cost solution, Elegen and Nutcracker Therapeutics aim to democratize PCTs, making them accessible to more developers and saving critical time for cancer patients, where even days can make a meaningful impact.

"Integrating cell-free DNA with cell-free biochip-based RNA production gives researchers and partners worldwide access to a more reliable, streamlined, and cost-effective platform to rapidly test and advance new therapies," said Matthew Hill, founder and CEO of Elegen. "By eliminating cells from the process, we can accelerate the development and evaluation of new therapeutic modalities, helping patients receive treatment as quickly as possible."

"We’re not just improving our manufacturing process, we’re laying the foundation to democratize PCTs with truly scalable solutions," added Benjamin Eldridge, co-founder and chief technology officer of Nutcracker Therapeutics. "Achieving that vision means giving developers the ability to produce clinical-grade RNA without investing hundreds of millions in infrastructure. This is a key step toward our mission of delivering scalable, low-cost, and rapid formulated RNA manufacturing for individualized therapies."

Elegen’s cell-free ENFINIA DNA with an unparalleled combination of speed, length, accuracy and complexity integrates seamlessly with Nutcracker Therapeutics’ existing RNA-based PCT development process, which leverages artificial intelligence and machine learning technologies through its CodonCracker RNA design software, the NMU-Symphony microfluidics biochip-based system, and ProcessVision technology for real-time performance and quality monitoring. Combined, Elegen and Nutcracker Therapeutic’s technologies enable the efficient, flexible, and GMP-ready production of individualized nanoparticle-formulated RNA therapeutics.

CEL-SCI Announces Pricing of $5.7 Million Offering Priced At-the-Market Under NYSE American Rules

On July 11, 2025 CEL-SCI Corporation ("CEL-SCI" or the "Company") (NYSE American: CVM), a clinical stage cancer immunotherapy company, reported the pricing of a best-efforts offering of 1,500,000 shares of its common stock (Press release, Cel-Sci, JUL 11, 2025, View Source [SID1234654353]). Each share of common stock is being sold at an offering price of $3.82 per share, priced at-the-market under NYSE American rules. Total gross proceeds from the offering, before deducting the placement agent’s fees and other offering expenses, are expected to be approximately $5.7 million. The offering is expected to close on July 14, 2025, subject to satisfaction of customary closing conditions.

The Company intends to use the net proceeds from the offering to fund the continued development of Multikine, general corporate purposes, and working capital.

ThinkEquity is acting as the sole placement agent for the offering.

The securities will be offered and sold pursuant to a shelf registration statement on Form S-3 (File No. 333-265995), including a base prospectus, filed with the U.S. Securities and Exchange Commission (the "SEC") on July 1, 2022, and declared effective on July 15, 2022. The offering will be made only by means of a written prospectus. A final prospectus supplement and accompanying prospectus describing the terms of the offering will be filed with the SEC on its website at www.sec.gov. Copies of the prospectus supplement and the accompanying prospectus relating to the offering may also be obtained, when available, from the offices of ThinkEquity, 17 State Street, 41st Floor, New York, New York 10004.

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 an offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.