On September 22, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (TSX: APS; OTC: APTOF), a clinical-stage precision oncology company developing a tuspetinib (TUS) based triple drug frontline therapy to treat patients with newly diagnosed acute myeloid leukemia (AML), reported that it has entered into a US$11.9 million loan Amended Facility Agreement ( "Facility Agreement") with Hanmi Pharmaceutical Co. Ltd. ("Hanmi") (Press release, Aptose Biosciences, SEP 22, 2025, View Source [SID1234656139]).

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The Facility Agreement is uncommitted and administered through multiple advances until December 31, 2025, and will be used to fund Aptose’s business and clinical operations expenses reasonably related to the advancement of TUS. Aptose has not yet received funds from this Facility Agreement but expects the first advance soon. This Facility Agreement has been amended and restated from the prior June 2025 Facility Agreement between Hanmi and Aptose. No single advance shall be for an amount in excess of US$2,000,000, and any unpaid principal amount with respect to each advance shall accrue interest at six percent (6%) per annum. The Facility Agreement contains customary affirmative and negative covenants and securities that are subject to a number of limitations and exceptions.

In addition, Aptose has received the final advance of US$1.4 million for a total of US$8.5 million from the prior June 2025 Facility Agreement with Hanmi (press release here).

"The growing body of positive data on tuspetinib demonstrates that, by adding TUS to the VEN+AZA standard of care in AML, we can safely and more effectively treat some of AML’s largest patient populations, in addition to subgroups having adverse genetics defined by FLT3, NKRAS, and TP53 genes," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose. "We are very grateful for Hanmi’s support for the continued development of an important new treatment in the AML armamentarium."

Tuspetinib is a convenient once daily oral agent that potently targets SYK, mutated and wild type forms of FLT3, mutated KIT, JAK1/2, and RSK2 kinases, while avoiding many typical toxicity concerns observed with other agents. The ongoing TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of azacitidine and venetoclax in newly diagnosed patients with AML who are ineligible to receive induction chemotherapy. Aptose recently reported data from the first three dose cohorts that have demonstrated safety, CRs and minimal residual disease (MRD) negativity across patients with diverse mutations. The early data showed that 9 out of 10 patients responded to the TUS triplet therapy, with 100% complete remission (CR/CRh)1 achieved in the 80mg and 120mg cohorts. Notably, patients with difficult-to-treat mutations in TP53, RAS and FLT3 genes also achieved a 100% CR/CRh rate (press release here).

The September 2025 Loan Facility Agreement constitutes a "related-party transaction" within the meaning of Multilateral Instrument 61-101 – Protection of Minority Security Holders in Special Transactions ("MI 61-101") as Hanmi is a related party of the Company under Canadian securities laws. However, the Company is relying on the exemption from the formal valuation and minority shareholder approval requirements contained in MI 61-101 on the basis of the "financial hardship" exemption therein. In its consideration and approval of the September 2025 Loan Facility Agreement, the Board of Directors of the Company, acting in good faith and having taken into account the liquidity, financial position and cash needs of the Company, the alternatives available to the Company, relevant benefits, risks and other factors, including the relative impacts on applicable stakeholders, and such matters they considered relevant or appropriate, unanimously determined that entering into the September 2025 Loan Facility Agreement will result in an improvement of the Company’s financial position, and that the terms of the September 2025 Loan Facility Agreement are reasonable in the circumstances of Aptose. The Company did not file a material change report 21 days prior to the execution of the September 2025 Loan Facility Agreement as details of the September 2025 Loan Agreement were unknown at such time.

On September 22, 2025 Alligator Bioscience (Nasdaq Stockholm: ATORX), a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs, reported final results from the OPTIMIZE-1 trial evaluating its lead asset, mitazalimab, in combination with mFOLFIRINOX chemotherapy in patients with previously untreated metastatic pancreatic cancer (Press release, Alligator Bioscience, SEP 22, 2025, View Source [SID1234656138]).

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The OPTIMIZE-1 study has consistently demonstrated promising clinical activity throughout its course. The final read-out confirms that mitazalimab in combination with standard chemotherapy continues to deliver encouraging efficacy outcomes, with durable responses and survival rates that compare favorably to historical benchmarks.

These results further strengthen the rationale for advancing mitazalimab into a pivotal Phase 3 trial in metastatic pancreatic cancer.

After a median follow-up of 33 months, two patients remained on treatment and 8 in long-term survival follow up resulting in a 30-month overall survival (OS) rate of 21%. The final readout confirms data maturity, demonstrating both primary and secondary efficacy endpoints that compare favorably with historical controls. As previously reported, the objective response rate (ORR) was 54.4% (42.1% confirmed). The median duration of response was 12.6 months, with a median progression-free survival (PFS) of 7.8 months. Median OS reached 14.9 months, with OS rates of 58%, 37%, 26%, and 21% at 12, 18, 24, and 30 months, respectively—an unprecedented outcome in this hard-to-treat cancer. These results underscore a durable benefit, with a meaningful proportion of patients achieving long-term survival beyond two years.

"The final OPTIMIZE-1 results reinforce our belief that mitazalimab has the potential to become a transformative treatment option for patients with pancreatic cancer, a disease with very limited therapeutic advances in decades," said Søren Bregenholt, CEO at Alligator Bioscience. "OPTIMIZE-1 has now successfully fulfilled it purpose and will be winding down following these final results. Hence, the costs continue to decrease as clinical sites close, while we remain well prepared to initiate a confirmatory Phase 3 trial together with a partner. We look forward to bringing this important therapy one step closer to patients."

On September 22, 2025 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company") reported that the Journal for ImmunoTherapy of Cancer (JITC) has published a new peer-reviewed article providing evidence of a positive combination effect of AIM’s drug Ampligen and interferon-alpha on tumor growth and subsequent subject survival (Press release, AIM ImmunoTech, SEP 22, 2025, View Source [SID1234656137]).

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The paper concluded that the ability of systemic chemokine modulation to eliminate the PD-1-resistance of cold tumors indicates that intratumoral cytotoxic t-lymphocyte accumulation, rather than tumor immunogenicity, is the key factor limiting the therapeutic effectiveness of immune checkpoint inhibitors. These data suggest a broad therapeutic potential of tumor microenvironment reprogramming strategies.

The article, titled "Synergy between TLR3-ligand and IFN-α in the transient sensitization of ‘Cold’ tumors to PD-1 blockade and the induction of systemic immunity," was published in JITC on September 18.

On September 22, 2025 Fierce biotech reported that from advancing radically new therapies to refining existing modalities, this year’s Fierce 15 companies are pushing the envelope and giving us a reason for optimism (Press release, Alterome Therapeutics, SEP 22, 2025, View Source [SID1234656136]).

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This year has been chock-full of challenges, ranging from a seemingly never-ending biotech bear market to deep uncertainty surrounding regulatory and international policies. Yet, unmet need still fuels biotech, with companies risking it all in hopes of bringing new medicines to patients.

Welcome to this year’s best in biotech. These biotechs were carefully selected from hundreds of nominees and represent the most innovative and visionary companies leading the pack—even, or maybe especially, through unpredictable conditions.

This year, the Fierce 15 recognizes biotechs across continents and indications, including companies working to battle cancer, neurodegeneration, rare diseases, autoimmune conditions and more.

This is the crème de la crème working on both next-generation drugs and never-before-seen modalities. While the organizations differ across methods and therapeutic areas, there’s one main common thread: They’re all challenging old ways of working.

The 2025 class is defined by resilience, diversity in both strategy and leadership, and treatments that hold life-changing potential for underserved patients around the world.

Read on to meet the companies—and leaders—redefining biotech. We are pleased to present Fierce Biotech’s 2025 Fierce 15.

Alterome Therapeutics

Targeting the genetic alterations that cause cancer while sparing healthy cells

CEO: Jung Choi
Founded: 2021
Based: San Diego
Clinical focus: Breast and endometrial cancers, colorectal cancer, pancreatic ductal adenocarcinoma, non-small cell lung cancer, solid tumors

What makes Alterome fierce: Alterome Therapeutics was founded with a mission to discover precision medicines that could potentially treat what CEO Jung Choi describes as "some of the scariest cancers out there," including cancers of the pancreas, colon and lungs.

As its name suggests, Alterome’s approach is centered on developing drugs that aim to attack the genetic mutations that cause cancer, while trying to minimize side effects to the body’s healthy cells.

The company’s work is driven by three main factors, Choi said in an interview with Fierce Biotech: "a very deep understanding of the cellular pathways that drive cancer," a fast-paced drug development approach rooted in advanced chemical structure and physics-based design—powered by its Kraken computational chemistry platform—and a team of "relentless" scientists at the core of it all.

"So, that’s how we’ve been able to go from idea to clinic in just three and a half years, with two potentially best-of-their-kind cancer medications," she said.

Those two candidates are now in phase 1 trials. The first is a KRAS selective inhibitor that Choi described as "the Goldilocks of KRAS," because it aims to bridge the gap between KRAS inhibitors that only target specific mutations and those that take aim at all forms of RAS, leading to unwanted toxicities.

Alterome’s take on the approach, then, is an attempt at "hitting KRAS very selectively, but also inhibiting nearly all, if not all, of the KRAS mutations potently and durably," she said, while also inhibiting KRAS whether active or inactive and boasting "very good druglike properties."

The company believes ALTA3263 is "the best KRAS inhibitor that hits all four characteristics," according to Choi. It’s being studied in colorectal, pancreatic and non-small cell lung cancers.

The other candidate, ALTA2618, is a covalent AKT1 E17K mutation-selective inhibitor that Alterome has developed to target only the mutant form of AKT that drives cancer, while leaving the benign form of the protein alone.

"What’s exciting to us is that, as far as we know, we are the first investigational therapy that’s in the clinic with this approach," Choi said, adding that ALTA2618 is being studied in patients with hormone-positive breast cancer as well as endometrial, ovarian and other AKT1-driven cancers.

Alterome is hoping to keep up the fast pace of development. The company plans first to generate monotherapy data for both candidates in the "not-too-distant future," per Choi, before "moving very quickly" into testing them as part of combination therapies, then taking those results to the FDA for the go-ahead to start registrational studies.

The company’s current and future plans are being helped along by VC funding that most recently included a series B round led by Goldman Sachs Alternatives and closed in the spring of 2024 with $132 million. Like any biotech startup, Choi said Alterome will "do more financing as time goes on," drawing in new backers based on "very meaningful clinical milestones."

Choi joined Alterome earlier this year, fresh off a stint as entrepreneur in residence at Third Rock Ventures and following various roles leading corporate development at Gilead Sciences, Chimerix, InterMune—until it was purchased by Roche in 2014—and Global Blood Therapeutics, through its own 2022 acquisition by Pfizer.

On September 20, 2025 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a late-stage immunotherapy company targeting cancer and autoimmune diseases, reported the initiation of an investigator-initiated Phase II trial evaluating neoadjuvant eftilagimod alfa (efti) administered subcutaneously as monotherapy and then in combination with standard-of-care chemotherapy prior to surgery in patients with early-stage HR+/HER2-negative breast cancer (Press release, Immutep, SEP 20, 2025, View Source [SID1234656122]).

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The study will treat up to 50 evaluable patients in a two-stage design and will be primarily funded by grants and The George Washington (GW) University Cancer Center. Immutep will provide efti at no cost, technical support, and limited funding that falls within its existing budget. The trial will be led by Principal Investigator, Pavani Chalasani, MD, MPH, Division Director of Hematology and Medical Oncology at the GW Cancer Center and a leader of the GW Cancer Center Breast Cancer clinical research team.

Dr. Chalasani stated, "Given my clinical experience with efti in the AIPAC-003 study coupled with promising data from additional trials evaluating efti in metastatic breast cancer settings, we look forward to evaluating this unique immunotherapy at earlier stage disease in patients with HR+/HER2 -ve breast cancer. As a novel neoadjuvant immunotherapy option, efti’s powerful and safe activation of a broad anti-cancer immune response in combination with chemotherapy may lead to high rates of pathologic complete responses, the primary endpoint of this study. Additionally, we are hopeful that efti’s immune activation in these patients with early stage cancer who have stronger immune systems may lead to improved disease free survival."

Efti’s targeting and unique activation of powerful antigen-presenting cells via MHC Class II leads to a broad anti-cancer immune response. This includes the activation and proliferation of cytotoxic CD8+ T cells that can be armed in vivo with chemotherapy-induced tumour antigens, as well as numerous other immune cells and cytokines enhancing the immune system’s ability to fight cancer. This novel immunotherapy has yielded encouraging clinical results in metastatic disease and earlier stage disease in its initial trial as a neoadjuvant treatment in soft tissue sarcoma.

Immutep CEO, Marc Voigt added, "We are thankful for the interest and investment by academia in the United States and elsewhere to evaluate the promise of efti at earlier-stage disease. This trial helps us cost-efficiently expand our clinical pipeline for neoadjuvant efti in areas of high unmet need. Our belief is this novel immune system activator can play a meaningful role in metastatic settings and in the ongoing expansion of immunotherapy into neoadjuvant settings to fight cancer."

The goal of this multi-center study led by the GW Cancer Center is to determine pathological complete response (pCR) after neoadjuvant efti treatment and neoadjuvant chemotherapy (NAC). This is a single-arm interventional trial in patients with early-stage HR+/HER2 -ve breast cancer (Stage I-III) who are eligible for NAC. Enrolled patients will be treated with efti monotherapy for three weeks and then start NAC in combination with efti. For more information, visit clinicaltrials.gov (NCT07102940).

About Eftilagimod Alfa (efti)
Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA).