On April 28, 2025 The Management Board of 4SC AG ("4SC") (Frankfurt Stock Exchange, Prime Standard: VSC; ISIN: DE000A14KL72) reported by the European Medicines Agency (EMA) that, based on the review of the final data and the company’s responses to the Day-180 Assessment Report, 4SC has been invited to an oral discussion before the Committee for Medicinal Products for Human Use (CHMP) at its meeting in late May (Press release, 4SC, APR 28, 2025, View Source [SID1234652255]). Following this meeting, the CHMP is expected to issue a decision on whether to issue a positive or negative recommendation on the company’s Marketing Authorization Application (MAA) for resminostat (Kinselby) in the EU.

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!

Information and explanations of the issuer regarding this announcement:

Future-oriented information
This release contains certain forward-looking statements that involve risks and uncertainties and reflect 4SC’s assessment as of the date hereof. Such forward-looking statements are neither promises nor guarantees, but are subject to numerous risks and uncertainties, many of which are beyond 4SC’s control, which could cause actual results to differ materially from those contemplated by such forward-looking statements. 4SC expressly disclaims any obligation to update or revise any forward-looking statements to reflect changed expectations or new events, conditions, or circumstances on which any such statements are based.

On April 28, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported preclinical results with ATNM-400 in prostate cancer models presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, APR 28, 2025, View Source [SID1234652253]). ATNM-400 is a novel, non-PSMA targeting, first in class targeted radiotherapy utilizing the Actinium-225 (Ac-225) radioisotope that Actinium is evaluating in prostate cancer models prior to and following treatment with Pluvicto. Pluvicto (Lu-177-PSMA-617) is a prostate-specific membrane antigen (PSMA) directed radiotherapy radiolabeled with the beta-particle emitter, Lutetitium-177 (Lu-177) is approved for patients with metastatic castration-resistant prostate cancer. Pluvicto is marketed and sold by Novartis and generated sales of $1.39 billion in 2024.

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 vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

ATNM-400 is a highly innovative, first-in-class prostate cancer candidate in comparison to Pluvicto and the majority of radiotherapies in development for prostate cancer which target PSMA and are either non-differentiated or barely differentiated, as it targets a distinct non-PSMA receptor. The receptor specifically targeted by ATNM-400 is highly expressed in metastatic castration-resistant prostate cancer (mCRPC) and continues to be expressed at a high level even after Pluvicto treatment which does not appear to impact target expression levels. ATNM-400 leverages the alpha-particle emitter Ac-225, which is more potent than Lu-177, can cause lethal double-stranded irreversible DNA breaks, and has a shorter path length that could result in fewer off-target effects.

Key Data and Highlights From the ATNM-400 AACR (Free AACR Whitepaper) Presentation

In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

In mice bearing Pluvicto-failed tumors, ATNM-400 was administered on day 14 following Pluvicto treatment, demonstrating robust antitumor activity and tumor growth inhibition in Pluvicto- resistant tumor models.

Expression of the target receptor for ATNM-400 persists following Pluvicto therapy and ATNM-400 demonstrates sustained tumor control after Pluvicto stops working

ATNM-400 demonstrated greater efficacy than Pluvicto in prostate cancer models with 99.8% tumor growth inhibition achieved with a single 40 µCi/kg dose of ATNM-400 supporting its potential to be offered as an alternative option

ATNM-400 internalizes rapidly, exhibiting potent cytotoxicity and prostate cancer cell killing via double strand DNA breaks that are produced by the Ac-225 alpha-particle emitting radionuclide payload of ATNM-400

Biodistribution analyses showed sustained uptake in the tumor up to the 216-hour time point, with rapid clearance from the blood by the 48-hour time point and clearance from essential organs including the kidneys, intestines and liver

ATNM-400 was well tolerated with body weight recovery and no apparent toxicity at both doses evaluated in vivo
Sandesh Seth, Actinium’s Chairman and CEO, said, "We are thrilled to unveil these exciting results demonstrating the transformative therapeutic potential of ATNM-400. There is a significant unmet need for a therapy that can address patients who are treated with Pluvicto and progress, which we only expect to increase following the recent approval of Pluvicto in the earlier line, pre-taxane setting. Consistent with our focus on leading-edge innovation, ATNM-400 is highly novel given it is a non-PSMA target receptor, which is highly expressed in mCRPC, and as we have presented at AACR (Free AACR Whitepaper), continues to be expressed following Pluvicto therapy. ATNM-400 capitalizes on the potency and precision of the Ac-225 isotope payload that can overcome resistance via lethal double strand DNA breaks. Our enthusiasm for ATNM-400 was validated by the significant interest this data received at AACR (Free AACR Whitepaper) and we look forward to validating the potential of this exciting radiotherapy candidate as we advance its development with additional data expected later this year".

The ATNM-400 AACR (Free AACR Whitepaper) presentation is available for viewing on the Presentations & Webinars page of Actinium’s website HERE.

Title: ATNM-400 is a novel Actinium-225 antibody radioconjugate with strong efficacy in preclinical models of prostate cancer
Abstract Number: 578

On April 28, 2025 TuHURA Biosciences, Inc. (NASDAQ:HURA) ("TuHURA"), a Phase 3 immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, reported on poster presentations of Kineta Inc.’s ("Kineta") KVA12123 novel anti-VISTA antibody and TuHURA’s IFx-Hu2.0 in advanced melanoma and at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL (Press release, TuHURA Biosciences, APR 28, 2025, View Source [SID1234652249]).

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 the first poster presentation, (CT041/20) TuHURA and Kineta provided updated results from VISTA-101, a Phase I-II first-in-human study of KVA12123 alone and in combination with pembrolizumab in patients with advanced solid tumors (NCT05708950). The poster, was presented by Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta. KVA12123 was found to be generally safe and well tolerated in all monotherapy and combination arms, with no dose-limiting toxicities observed. Additionally, KVA12123 demonstrated a favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile at all dose levels, including:

At 1,000mg every two weeks, KVA12123 demonstrated greater than dose proportional PK profile exceeding 90% VISTA receptor occupancy, providing important PK data for determining recommended Phase 2 dose.
No dose limiting toxicities were observed in the study, including at the 1,000mg dose level, among the 24 patients treated in the monotherapy or in the 17 patients in the combination with pembrolizumab arms
"We are pleased to have Thierry present the latest data from the KVA12123 program, a valuable drug candidate that TuHURA will acquire following the closure of the proposed merger with Kineta which is currently targeted for the end of Q2 2025. TuHURA’s exclusivity payment last July allowed Kineta the ability to restart and complete the Phase I study providing important data regarding receptor occupancy and other PK, PD and translational biomarker data at the previously unstudied 1,000mg dose level. The study demonstrated in excess of 90% VISTA receptor occupancy over the entire Q2W dosing interval where PK simulations would predict similar receptor occupancy even at 750mg Q2W dosing, which we believe will be the recommended Phase 2 dose and schedule", stated James Bianco, M.D., President and Chief Executive Officer of TuHURA Biosciences.

Dr. Bianco continued, "Our primary interest in VISTA is its potential in immunologic tolerance in a variety of blood related cancers. Recent scientific data demonstrates that NPM1 mutation, present in 30% to 35% of patients with acute myeloid leukemia (AML) results in the high expression of VISTA on leukemic blasts. This is believed to be the mechanism by which leukemia escapes immune recognition and attack and is responsible for high rate of treatment failures in AML. We look forward to evaluating the VISTA inhibiting antibody in a Phase 2 randomized study in relapsed AML, which we expect to initiate in the fourth quarter of 2025 based on the anticipated closing of the proposed merger with Kineta."

TuHURA also announced that the Markowitz Lab at Moffitt Cancer Center also presented a poster of TuHURA’s IFx-Hu2.0 in patients with advanced treatment refractory Melanoma who, like patients in TuHURA’s Phase 1b Merkel cell carcinoma trial, progressed while on CPI therapy. The data demonstrated that, among heavily pre-treated patients with advanced Melanoma who were resistant to anti-PD-1-based therapy, following IFx-Hu2.0, three of four patients achieved clinically meaningful, durable anti-tumor responses following re-administration of a CPI.

"Demonstration of the development of antibody specific response to the Emm55 bacterial protein expressed on the surface of the tumor cell following IFx-Hu2.0 in the phase 1 study and an abscopal effect in murine model of melanoma is consistent with the data generated in patients with advanced cutaneous malignancies like melanoma or Merkel cell carcinoma," noted Dr. Bianco. "We look forward to that anticipated initiation of our Phase 3 accelerated approval trial in first line treatment of patients with advanced or metastatic Merkel cell carcinoma targeted for later this quarter."

In the second poster presentation relating to IFx-Hu2.0 entitled: "Mechanistic Insights into IFx- Hu2.0 Responses in the First Human Trial After Prior Anti-PD-1 Therapy Failure," (3428/23) IFx-Hu2.0’s first-in-human study demonstrated stimulation of an innate immune response, with increased T cell and B cell production in peripheral blood compared to tumor tissue. This innate immune activation underscores the potential of IFx-Hu2.0 to generate tumor specific activate T and B cells for patients who are resistant to anti-PD-1 CPIs. Additionally, IFx-Hu2.0 was generally safe and well tolerated, with only mild Grade 1 and Grade 2 adverse events, largely injection site reactions.

As previously announced, on December 11, 2024, TuHURA entered into a definitive agreement with Kineta, Inc. (OTC Pink: KANT) ("Kineta"), in which TuHURA agreed to acquire Kineta, including the rights to Kineta’s novel KVA12123 antibody, for a combination of cash and shares of TuHURA common stock via a merger transaction upon the terms and conditions and subject to the conditions set forth in TuHURA’s Form 8-K filed on December 12, 2024. The merger is currently targeted to close in Q2 2025 pending the satisfaction of certain closing conditions.

On April 28, 2025 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported that a presentation of new data supporting the immune component of amezalpat’s purported dual mechanism of action that reinforces its potential as a novel cancer treatment at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Tempest Therapeutics, APR 28, 2025, View Source [SID1234652248]).

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!

"The data presented at the AACR (Free AACR Whitepaper) Annual Meeting show that amezalpat reduced tumor promoting immunosuppression by M2 macrophages and T regulatory cells resulting in immune activation. These data support the immune-mediated anti-cancer activity of the proposed dual MOA of amezalpat," said Sam Whiting, M.D., Ph.D., chief medical officer and head of R&D at Tempest, "and are consistent with clinical data showing promising results in patients with HCC, RCC and CCA including in combination with approved immunotherapy. The results reinforce amezalpat’s novel and potentially first-in-class profile as a cancer therapy."

Amezalpat is an inhibitor of PPAR-alpha, the key regulator of fatty acid oxidation (FAO), which is a key metabolic pathway used by immunosuppressive macrophages and regulatory T cells (Tregs). Both cell populations are associated with poor prognosis in multiple cancer indications. Data presented demonstrated that amezalpat inhibits the development of these cells from precursor populations and is associated with reduced mitochondrial mass, the site of FAO, in immunosuppressive macrophages. Additionally, treatment of Tregs or immunosuppressive macrophages with amezalpat in the presence of tumor and cytotoxic T cells decreases anti-inflammatory cytokine production, indicating blockade of immune suppression that likely contributes to the efficacy of amezalpat observed in clinical trials.

About Amezalpat

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Data suggests that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In a global randomized phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the amezalpat arm showed clinical superiority across multiple study endpoints, including overall survival in both the entire population and key subpopulations, when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by additional positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors, including renal cell carcinoma and cholangiocarcinoma.

On April 28, 2025 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that preclinical efficacy of SLS009 in TP53 mutated Acute Myeloid Leukemia (AML) cells are being presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) taking place from April 25th – 30th at McCormick Place Convention Center, Chicago, IL (Press release, Sellas Life Sciences, APR 28, 2025, View Source [SID1234652247]).

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!

Patients with TP53–mutated AML continue to face extremely poor outcomes, even with intensive chemotherapy or the addition of stem cell transplantation. Preclinical data suggest that SLS009, a highly selective CDK9 inhibitor, can induce apoptosis downstream of p53 by targeting critical proteins such as MCL-1 and survivin, regardless of p53 status. Immunoblot analysis reveals near-complete removal of these proteins in treated cells within 8 hours of exposure to SLS009. Furthermore, the treatment reduced TP53-mutated leukemia cell populations by up to 97% in combination with azacitidine–venetoclax, and by up to 80% as monotherapy.

"These findings are an exciting step forward in addressing one of the most challenging subsets of AML," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The ability of SLS009 to overcome TP-53 driven resistance in preclinical models, combined with the positive data we have seen in our ongoing Phase 2 AML program, including a response in a patient with a TP53 mutation, gives us hope that we may one day offer an effective therapeutic option to patients with AML who have long been underserved."

SLS009 is currently in Phase 2 clinical trials in patients with relapsed or refractory (r/r) AML following venetoclax-based regimens, including patients with TP53-mutated leukemia. Recently announced data revealed that r/r AML patients receiving 30 mg of SLS009 BIW achieved a mOS of 8.8 months for all patients, while the mOS in AML myelodysplasia-related-changes (MRC) patients reached 8.9 months – far surpassing the historical benchmark of 2.5 months. Among patients with mutation ASXL1, 4/6 (67%) responded; among those with RUNX1 3/5 (60%) responded, and among those with TP53 1/3 (33%) responded. In addition, there were 3 patients with adverse karyotypes, and 1 responded.

"Over the past decade we’ve seen significant progress in the treatment of AML, particularly with the introduction of the venetoclax/azacitidine regimen, the use of targeted agents, and safer application of haploidentical stem cell transplants," said Dr Phillip Amrein, MD, Clinical Investigator, Massachusetts General Hospital, Assistant Professor of Medicine Harvard Medical School, the senior author of the study. "Yet, leukemias characterized by TP53 remain a major area of unmet need, with poor outcomes even with bone marrow transplantation. The preclinical findings suggest that CDK9 inhibition might have the potential to overcome this resistance and restore sensitivity to existing therapies, offering a promising new path forward for high-risk patient populations."

Poster presentation details:

Title: CDK9 inhibition enhances apoptosis of TP53 mutated AML when combined with standard chemotherapy

Session Date and Time: Monday, April 28, 20025, 9:00 AM to 12:00 noon

Session Title: CDK9 inhibition enhances apoptosis of TP53 mutated AML when combined with standard chemotherapy

Location: Poster Section 17

Poster Board #: 1626

The poster will be available on SELLAS websites following the session.

SLS009 is currently being investigated in a Phase 2 open-label, single-arm, multi-center study designed to evaluate the safety, tolerability, and efficacy of SLS009 in combination with venetoclax and azacitidine, including AML patients with ASXL1 mutations. Initial clinical safety and efficacy data are available. In addition, the study aims to identify biomarkers for the target patient population and enrichment for further trials. For more information on the study, visit clinicaltrial.gov identifier NCT04588922.