On June 20, 2025 Aptevo Therapeutics Inc. ("Aptevo" or the "Company") (Nasdaq:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported the addition of preclinical candidate APVO455 to its growing portfolio of CD3-directed candidates built on the CRIS-7 derived CD3 binding domain-an approach demonstrating compelling potential across both hematologic and solid tumors (Press release, Aptevo Therapeutics, JUN 20, 2025, View Source [SID1234654025]).

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With this announcement, Aptevo now has a suite of three CD3-engaging molecules in development. All three share the same CRIS-7 derived binding domain with a low cytokine release profile. In addition, APVO455 and APVO442 contain CD3 binding domains that are optimized for targeting solid tumors. All three molecules are designed to drive tumor-specific immune activation while limiting systemic toxicity. The suite includes:

Mipletamig , a CD123 x CD3 bispecific currently in Phase 1b/2 for frontline AML, where 85% of evaluable frontline patients across two trials have achieved remission in combination with standard of care. No cytokine release syndrome (CRS) has been observed in the first two trial cohorts of the ongoing RAINIER trial

APVO442 , a PSMA x CD3 candidate targeting prostate cancer, currently in preclinical development

And now APVO455 , a Nectin-4 x CD3 bispecific developed to address multiple solid tumor types

"With APVO455, we are rounding out a purposefully designed CD3 product suite that reflects both scientific rigor and clinical learning," said Marvin White, President and CEO of Aptevo. "Compelling mipletamig clinical results, where we have treated more than 100 patients across three trials, give us confidence that CRIS-7 is a critical differentiator. Our molecules behave predictably, drive selective activation and are emerging from a shared design strategy grounded in real-world human data."

Mr. White continued, "Ultimately, this design choice has yielded a compelling safety profile in the clinic, as seen with mipletamig, and supports broader application across indications where tolerability remains a barrier to effective T-cell engagement."

About APVO455: Advancing Nectin-4 T-cell Targeting in Solid Tumors

APVO455 is a preclinical Nectin-4 x CD3 bispecific T-cell engager designed for tumors such as bladder, breast, NSCLC, and head and neck cancers, where Nectin-4 is highly expressed. Unlike other approaches that restrict activity to acidic tumor environments or rely on activated T-cells, APVO455 is designed to avoid binding to or triggering T-cell activation in the periphery and do so only in the presence of Nectin-4 positive tumor cells, offering the potential for a broader therapeutic window and more consistent immune activation.

Looking Ahead

APVO455 represents the third CD3 bispecific in Aptevo’s portfolio and the sixth overall drug candidate in active development. The Company anticipates further expanding its CD3 suite in the future.

On June 20, 2025 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of nirogacestat, an oral gamma secretase inhibitor, as monotherapy for the treatment of adults with progressing desmoid tumors who require systemic treatment (Press release, SpringWorks Therapeutics, JUN 20, 2025, View Source [SID1234654023]). The European Commission (EC) will review the CHMP opinion and is expected to make a final decision regarding the approval in the third quarter of 2025.

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"The positive opinion from the CHMP reflects the meaningful benefits nirogacestat can offer patients in Europe where currently there are no approved treatment options," said Saqib Islam, Chief Executive Officer of SpringWorks. "We look forward to the European Commission’s decision as we strive to bring nirogacestat to desmoid tumor patients globally."

Nirogacestat previously received Orphan Drug designation from the European Commission for the treatment of soft tissue sarcoma. The CHMP opinion was based on the Marketing Authorization Application (MAA) for nirogacestat, which centered on results from the Phase 3 DeFi trial that were published in The New England Journal of Medicine.1 In DeFi, nirogacestat met the primary endpoint of improving progression-free survival (PFS), demonstrating a 71% lower risk of disease progression compared to placebo. Nirogacestat demonstrated a significant improvement in objective response rate as well as early and sustained improvements in patient-reported outcomes (PROs), including pain, physical functioning and overall quality of life.

Nirogacestat exhibited a manageable safety and tolerability profile. The most common adverse reactions reported in patients receiving nirogacestat were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.

"Desmoid tumors can have a profound impact on patients as well as their loved ones, and the positive CHMP opinion underscores the potential benefit of nirogacestat for these patients," Bernd Kasper, M.D., Ph.D., Professor, University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany, and principal investigator of the DeFi trial. "It is very encouraging that a significant number of people taking nirogacestat experienced reductions in their tumor size and also rapid and sustained relief of their desmoid tumor symptoms, including pain."

Nirogacestat is approved in the U.S. for the treatment of adults with progressing desmoid tumors who require systemic treatment.

About the DeFi Trial
DeFi (NCT03785964) was a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal Phase 3 trial that evaluated the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints included safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes (PROs). DeFi also included an open-label extension phase.

About Desmoid Tumors
Desmoid tumors are rare, aggressive, locally invasive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.2,3

Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females.4,5 It is estimated that there are 1,300-2,300 new desmoid tumor cases diagnosed per year in the European Union.6,7

Although desmoid tumors do not metastasize, they can be associated with recurrence rates of up to 77% after surgical resection.5,8 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention for most tumor locations requiring treatment.9,10

About Nirogacestat

Nirogacestat is an oral, selective, small molecule gamma secretase inhibitor approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. Nirogacestat is not approved for the treatment of any other indication in the United States, or for any indication in any other jurisdiction by any other health authority.

On June 20, 2025 Ratio Therapeutics Inc. (Ratio), a pharmaceutical company employing innovative technologies to develop best-in-class radiopharmaceuticals for cancer treatment and monitoring, and TerraPower Isotopes, a subsidiary of TerraPower, a leading nuclear innovation company, reported they entered into a supply agreement for the medical radioisotope actinium-225 (Ac-225) (Press release, Ratio Therapeutics, JUN 20, 2025, View Source [SID1234654022]). Under the agreement, TerraPower Isotopes would supply Ratio with quantities of non-cGMP Ac-225 for use to incorporate into or use in the development of Ratio’s radiopharmaceuticals.

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Ac-225 plays a vital role in the development of next-generation radiopharmaceuticals, serving as a powerful alpha-emitting isotope used in targeted cancer therapies. For Ratio, access to a reliable supply of Ac-225 is essential to advancing its pipeline based on its proprietary Trillium and Macropa platforms. Together, these platforms enable the design and development of novel radiopharmaceuticals that can selectively target and eradicate cancer cells, offering a powerful and targeted approach to cancer treatment.

"Securing a reliable supply of Actinium-225 is a critical step in advancing our pipeline of targeted alpha therapies," said John Babich, Ph.D., President and Chief Scientific Officer of Ratio. "This agreement with TerraPower Isotopes strengthens our ability to scale production and advance our Trillium and Macropa platforms, which are purpose-built to fully harness the therapeutic potential of Actinium-225 in targeted alpha therapies."

"TerraPower Isotopes is committed to increasing the global supply of Actinium-225 to support cancer treatment research and development," said Scott Claunch, President of TerraPower Isotopes. "We’re proud to work with Ratio Therapeutics to help realize the full potential of Actinium-225 in radiopharmaceuticals. Once linked to a disease-targeting molecule, Actinium-225 labeled drug products can be precisely delivered to cancerous tissues, where they emit high-energy alpha particles capable of destroying tumor cells while sparing surrounding healthy tissue, making it a potentially transformative treatment option for patients."

On June 20, 2025 Ratio Therapeutics Inc. (Ratio), a pharmaceutical company employing innovative technologies to develop best-in-class radiopharmaceuticals for cancer treatment and monitoring, and TerraPower Isotopes, a subsidiary of TerraPower, a leading nuclear innovation company, reported they entered into a supply agreement for the medical radioisotope actinium-225 (Ac-225) (Press release, Ratio Therapeutics, JUN 20, 2025, View Source [SID1234654022]). Under the agreement, TerraPower Isotopes would supply Ratio with quantities of non-cGMP Ac-225 for use to incorporate into or use in the development of Ratio’s radiopharmaceuticals.

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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

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Ac-225 plays a vital role in the development of next-generation radiopharmaceuticals, serving as a powerful alpha-emitting isotope used in targeted cancer therapies. For Ratio, access to a reliable supply of Ac-225 is essential to advancing its pipeline based on its proprietary Trillium and Macropa platforms. Together, these platforms enable the design and development of novel radiopharmaceuticals that can selectively target and eradicate cancer cells, offering a powerful and targeted approach to cancer treatment.

"Securing a reliable supply of Actinium-225 is a critical step in advancing our pipeline of targeted alpha therapies," said John Babich, Ph.D., President and Chief Scientific Officer of Ratio. "This agreement with TerraPower Isotopes strengthens our ability to scale production and advance our Trillium and Macropa platforms, which are purpose-built to fully harness the therapeutic potential of Actinium-225 in targeted alpha therapies."

"TerraPower Isotopes is committed to increasing the global supply of Actinium-225 to support cancer treatment research and development," said Scott Claunch, President of TerraPower Isotopes. "We’re proud to work with Ratio Therapeutics to help realize the full potential of Actinium-225 in radiopharmaceuticals. Once linked to a disease-targeting molecule, Actinium-225 labeled drug products can be precisely delivered to cancerous tissues, where they emit high-energy alpha particles capable of destroying tumor cells while sparing surrounding healthy tissue, making it a potentially transformative treatment option for patients."

On June 20, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported the pricing of a public offering consisting of 16,080,000 shares of common stock (or pre-funded warrants in lieu thereof) and Series E warrants to purchase up to 48,240,000 shares of its common stock, at a combined public offering price per share of common stock (or per pre-funded warrant in lieu thereof) and accompanying Series E warrants of $0.37 (Press release, Moleculin, JUN 20, 2025, View Source [SID1234654021]). The Series E warrants will have an exercise price of $0.37 per share, are exercisable upon stockholder approval, and will expire five years following the initial exercise date.

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The offering is expected to close on or about June 23, 2025, subject to customary closing conditions. Gross proceeds, before deducting placement agent fees and commissions and offering expenses, are expected to be approximately $5.9 million. The Company intends to use the net proceeds from the offering to advance Annamycin and its other two drug portfolios through clinical development, advancing the remainder of the existing portfolio through preclinical studies and into INDs or their equivalent, sponsoring research, and for working capital.

Roth Capital Partners is acting as exclusive placement agent of the offering. Maxim Group LLC is acting as financial advisor to the Company.

The securities described above are being offered pursuant to a registration statement on Form S-1 (File No. 333-287727), that was declared effective by the U.S. Securities and Exchange Commission ("SEC"), on June 20, 2025. The offering is being made only by means of a prospectus forming part of the effective registration statement relating to the offering. A preliminary prospectus relating to the offering has been filed with the SEC. Electronic copies of the final prospectus relating to and describing the terms of the offering may be obtained, when available, at the SEC’s website at www.sec.gov or by contacting Roth Capital Partners, LLC, 888 San Clemente Drive, Suite 400, Newport Beach, CA 92660 or by email at [email protected].

This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of these securities in any state or other 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 other jurisdiction.