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Koselugo recommended for approval in the EU by CHMP for plexiform neurofibromas in adults with neurofibromatosis type 1

On September 22, 2025 Astrazeneca reported that Koselugo (selumetinib), an oral, selective MEK inhibitor, has been recommended for approval in the European Union (EU) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in adult patients with neurofibromatosis type 1 (NF1) (Press release, AstraZeneca, SEP 22, 2025, View Source [SID1234656140]).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from KOMET, the largest and only placebo-controlled global Phase III trial in this patient population, which were presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and published in The Lancet.1

In the primary analysis of the trial, Koselugo showed a statistically significant objective response rate (ORR) of 20% (n=14/71, 95% CI: 11.2, 30.9) compared to 5% with placebo (n=4/74, 95% CI: 1.5, 13.3; p=0.01) by cycle 16.1

NF1 is a rare, progressive, genetic condition usually diagnosed in early childhood, but often progressing into adulthood, that can impact every organ system.2,3 Up to 50% of people living with NF1 may develop a type of non-malignant tumour called PN that may affect the brain, spinal cord and nerves.3,4 PN may appear later in a person’s life and can grow and become large, leading to pain, disfigurement and muscle weakness, among other debilitating symptoms.3,4

Prof. Pierre Wolkenstein, MD, PhD, Head of the Department of Dermatology at Henri Mondor Hospital, APHP, Paris East University (UPEC), and National Coordinating Investigator of the KOMET trial in Europe, said: "For adults with NF1, tumour growth doesn’t stop at childhood and can rapidly progress or develop into adulthood, impacting physical, emotional and social well-being. The positive recommendation by the CHMP for Koselugo in adults underscores the urgent need for additional targeted treatments for this patient population. When approved, Koselugo could offer a treatment option for adult patients and continuity of care across age groups, supported by established clinical experience and practice among doctors managing this lifelong condition."

Marc Dunoyer, Chief Executive Officer, Alexion, said: "The CHMP positive opinion of Koselugo in adults with NF1 PN builds on more than a decade of global clinical and real-world experience, reflecting the unmatched body of evidence supporting the safety profile and efficacy of Koselugo. As demonstrated by the results from KOMET, the largest and only placebo-controlled, double-blind global Phase III trial in an adult population, we continue to advance the pioneering legacy of Koselugo, which set the treatment standard in NF1 PN, to reach even more people worldwide."

The safety profile of Koselugo in the KOMET Phase III trial was consistent with its known profile and established use in paediatric patients.1

Koselugo has been recently approved in Japan and other countries for the treatment of adult patients with NF1 who have symptomatic, inoperable PN based on data from the KOMET Phase III trial, and additional regulatory reviews are ongoing.

Notes

NF1
NF1 is a rare, progressive, genetic condition that is caused by a spontaneous or inherited mutation in the NF1 gene.2,3 NF1 is associated with a variety of symptoms, including soft lumps on and under the skin (cutaneous neurofibromas) and, in up to 50% of patients, tumours called plexiform neurofibromas (PN) may develop on the nerve sheaths.3,4 These PN can cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment and bladder or bowel dysfunction.3,4

KOMET
KOMET is a global Phase III randomised, double-blind, placebo-controlled, multicentre trial designed to evaluate the efficacy and safety of Koselugo in adults with NF1 who have symptomatic, inoperable PN. The trial enrolled 145 adults from 13 countries across North America, South America, Europe, Asia and Australia, with participants’ baseline characteristics, including gender and distribution of PN, reflective of the global adult NF1 patient population. Patients were enrolled and randomised to receive Koselugo or placebo (1:1) for 12 28-day cycles. Participants were required to have diagnosis of NF1, at least one symptomatic, inoperable PN measurable by volumetric MRI analysis, chronic PN pain score documented during screening, adequate organ and marrow function and stable chronic PN pain medication use at enrolment.1,5

The primary endpoint is confirmed objective response rate (ORR) by cycle 16 as assessed by ICR. ORR is defined as the percentage of patients with confirmed complete response (disappearance of PNs) or partial response (at least 20% reduction in tumour volume). Secondary endpoints include improved PN-related pain and health-related quality of life (HRQoL) at cycle 12.1,5

After 12 cycles, patients on placebo were switched to Koselugo and patients on Koselugo remained on treatment for an additional 12 cycles. Patients who had the opportunity to complete 24 cycles of treatment have the option to participate in a long-term extension period and continue to receive Koselugo.1,5

Koselugo
Koselugo (selumetinib) is a kinase inhibitor that blocks specific enzymes (MEK1 and MEK2), which are involved in stimulating cells to grow. In NF1, these enzymes are overactive, causing tumour cells to grow in an unregulated way creating so-called plexiform neurofibromas (PN). By blocking these enzymes, Koselugo slows down the growth of tumour cells and, therefore, the PN growth. 
 
Koselugo is approved in the US, EU, Japan, China and other countries for the treatment of certain paediatric patients with NF1 who have symptomatic, inoperable PN.

Koselugo is approved in Japan and other countries for the treatment of adult patients with NF1 who have symptomatic, inoperable PN, and additional regulatory reviews are ongoing

Koselugo has been granted Orphan Drug Designation in the US, EU, Japan and other countries for the treatment of NF1.

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Aptose and Hanmi Pharmaceutical Extend Loan Agreement to Continue Development of Tuspetinib in Triplet Therapy for AML

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]).

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.

Alligator announces final 30-month OPTIMIZE-1 results highlighting the potential of mitazalimab in metastatic pancreatic cancer

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]).

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."

AIM ImmunoTech Announces Publication of Journal Article On the Positive Effect of Ampligen and Interferon-Alpha on Tumor Growth

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]).

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.

Alterome Therapeutics, Inc. named one of Fierce Biotech’s 2025 Fierce 15

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]).

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.