On September 22, 2025 OGT, a leading global provider of genomic diagnostic and research solutions, reported that the U.S. Food and Drug Administration (FDA) has granted their De Novo Classification Request for the CytoCell KMT2A Breakapart FISH Probe Kit PDx as a companion diagnostic (CDx) for Syndax’s first-in-class menin inhibitor, REVUFORJ (revumenib) (Press release, Sysmex, SEP 22, 2025, View Source [SID1234656163]). Revuforj is FDA approved for the treatment of relapsed or refractory (R/R) acute leukaemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and paediatric patients one year and older.

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OGT’s CytoCell KMT2A Breakapart FISH Probe Kit PDx detects clinically relevant rearrangements that occur in patients with acute leukaemia, providing a robust, accessible, rapid turnaround test for KMT2Ar detection that will maximize the ability for clinicians to quickly identify patients who may be eligible for treatment with Revuforj. It is estimated that more than 95% of patients with KMT2Ar acute leukaemia have a KMT2A translocation, a type of rearrangement that occurs when part of one chromosome breaks and fuses to a different chromosome.

"We are delighted that our CytoCell KMT2A Breakapart FISH Probe Kit PDx has received marketing authorization as a CDx for Revuforj." said Dr. Leila Luheshi, VP of Pharma Partnering at OGT. "The development and subsequent authorization of this new CDx is an important demonstration of the skill and commitment of our clinical scientists and regulatory specialists to deliver safe and effective diagnostics for patients with one of the most devastating forms of leukaemia."

Steve Chatters, OGT’s EVP of Regulatory and Medical Affairs noted "Our strong foundation in haematology diagnostics has been a key factor in our success bringing the KMT2Ar CDx to market as a Class II device, as opposed to the more common Class III classification for companion diagnostics. We have decades of experience developing regulated FISH products, gained from our prior development of IVDR-certified and FDA-cleared FISH probes. Combined with our extensive customer partnerships in haematology labs in the USA, we have refined insights into the application of these products and are able to access a wealth of real-world data across a multitude of clinical and analytical factors, which is invaluable for product development. This is a core pillar of our success."

The emergence of precision therapies, such as the menin inhibitor Revuforj (an oral inhibitor of the menin–KMT2A interaction), offers new avenues for potentially improving outcomes for patients with these challenging acute leukaemia cases.

"Accurately identifying acute leukaemia patients with KMT2Ar is a key factor in selecting appropriate therapeutic options for a group of patients who have traditionally had a very poor prognosis" said Adrian Smith, CEO of OGT. "We are optimistic that the authorization of OGT’s CDx will help this underserved patient group benefit from developments in precision oncology."

On September 22, 2025 Haystack Oncology, a Quest Diagnostics (NYSE: DGX) company, reported a research collaboration with the Rutgers Cancer Institute to evaluate the use of Haystack MRD, a highly sensitive circulating tumor DNA (ctDNA) minimal residual disease (MRD) test, to help optimize postoperative therapy decisions in patients with stage II/III non-small cell lung cancer (NSCLC) (Press release, Quest Diagnostics, SEP 22, 2025, View Source [SID1234656149]). Rutgers Cancer Institute together with RWJBarnabas Health is the state’s only National Cancer Institute-designated Comprehensive Cancer Center.

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"Trial of ctDNA Guidance to Determine Post Operative Radiation Therapy (PORT) for Minimal Residual Disease (MRD) for Lung Cancer: the MRD-PORT Trial (NCT06979661)" is a prospective phase II study that will use the Haystack MRD test to assess whether the presence of residual tumor DNA after surgery can help guide the use of radiation and systemic therapies.

"Circulating tumor DNA is a pivotal marker to figure out how best to individualize patient care for lung cancer," said Salma Jabbour, MD, Vice Chair of Clinical Research and Faculty Development, Department of Radiation Oncology and Associate Director Faculty Affairs and Development, Rutgers Cancer Institute. "Studying new ways to detect this marker are important for helping improve patient outcomes."

Personalizing postoperative therapy in NSCLC

The study will evaluate ctDNA in patients with stage II/III NSCLC in the adjuvant setting. Patients who test positive for ctDNA after surgery—indicating potential residual disease—will be considered for adjuvant radiation and systemic therapy, including chemotherapy, immunotherapy, or targeted therapy, based on tumor biology and clinical context.

"The ability to identify residual disease following curative-intent treatment opens the door to more precise, personalized interventions, moving us closer to truly individualized cancer care," said Dan Edelstein, Vice President and General Manager of Haystack Oncology. "While existing data supports the prognostic value of ctDNA in lung cancer, this innovative study will now address the question of how ctDNA-based testing can guide and optimize adjuvant treatment decisions."

The study is the second by Rutgers Cancer Institute involving Haystack MRD. In 2023, the two parties announced a study to evaluate the test for use in patients being treated for early-stage triple-negative breast cancer.

Why ctDNA MRD matters

A growing body of research underscores the potential role of ctDNA MRD tests to identify residual or recurring cancer in patients with solid tumors. In April 2025, a study1 published in The New England Journal of Medicine (NEJM) found that ctDNA testing, using Haystack MRD, was a "reliable liquid biopsy surrogate" that identified clinical complete response at a median of 1.4 months compared to over 6 months using imaging tests. Nearly all oncologists (96%) in a recent survey2 by Harris Poll for Quest Diagnostics said MRD testing has the potential to identify cancer recurrence earlier than other current methods. In August 2025, the FDA granted Breakthrough Device Designation to Haystack MRD for identifying MRD-positive patients with stage II colorectal cancer following curative-intent surgical treatment who may benefit from adjuvant therapy in accordance with therapeutic product labeling.

About Lung Cancer

Lung cancer is the leading cause of cancer-related deaths in the U.S3. Despite advances in surgery and systemic therapies, recurrence rates remain high, especially for patients with stage II and III NSCLC.4 Studies show that patients who test positive for ctDNA after surgery have dramatically worse progression-free survival and overall survival compared to ctDNA-negative patients.

On September 22, 2025 Sartar therapeutics reported it was recently granted an new orphan drug designation (ODD) by the U.S. Food & Drug Administration (FDA) for the treatment of soft tissue sarcomas using its SAR003 drug candidate (Press release, Sartar Therapeutics, SEP 22, 2025, View Source [SID1234656150]). This is a great milestone for its team and a significant regulatory protection for SAR003 program. Sartar has previously received ODDs for SAR003 for the treatment of gastrointestinal stromal tumours (GIST) by both EMA and FDA.

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Now it has the ODD protection for SAR003 for the treatment of all soft tissue sarcomas in the US.

On September 22, 2025 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from the phase III evERA study evaluating investigational giredestrant in combination with everolimus in people with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy (Press release, Hoffmann-La Roche, SEP 22, 2025, View Source [SID1234656151]). The study met both co-primary endpoints, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in both the intention-to-treat and ESR1-mutated populations, compared with standard-of-care endocrine therapy plus everolimus. Overall survival (OS) data were immature, but a clear positive trend was observed. Follow-up continues to the next OS analysis. The giredestrant combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments, and no new safety signals were observed. This is the first positive head-to-head phase III trial investigating an all-oral selective oestrogen receptor degrader-containing regimen versus a standard of care combination.

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"These results show that the giredestrant combination provided a meaningful benefit for ER-positive breast cancer patients whose disease has progressed following treatment with a CDK inhibitor," said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. "We look forward to discussing these results with regulatory authorities with the goal of making this giredestrant-based regimen available to many people with advanced ER-positive breast cancer."

ER-positive breast cancer accounts for approximately 70% of breast cancer cases.2 Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity.3 Resistance to endocrine therapies, particularly in the post-CDK inhibitor setting, increases the risk of disease progression and is associated with poor outcomes.2,4 Combination therapies, such as giredestrant plus everolimus, could address this by targeting two different signalling pathways, with the potential for improved patient outcomes.3 Additionally, as an all-oral combination, this regimen could help minimise the impact of treatment on people’s lives without the need for injections.5

Our extensive giredestrant clinical development programme spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.

Data from the evERA study will be submitted to health authorities with the view of bringing this potential treatment option to patients as soon as possible.

About the evERA Breast Cancer study
evERA Breast Cancer [NCT05306340] is a phase III, randomised, open-label, multicentre study evaluating the efficacy and safety of giredestrant in combination with everolimus versus standard-of-care endocrine therapy in combination with everolimus in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase 4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.1

The co-primary endpoints are investigator-assessed progression-free survival in the intention-to-treat and ESR1-mutated populations, defined as the time from randomisation to the time when the disease progresses or a patient dies from any cause. The trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to 40% of people with ER-positive disease have ESR1 mutations4. Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and safety.1

About giredestrant
Giredestrant is an investigational, oral, next-generation selective oestrogen receptor degrader (SERD) and full antagonist.6

Giredestrant is designed to block oestrogen from binding to the oestrogen receptor (ER), triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.7,10-12

Giredestrant has an extensive clinical development programme and is being investigated in five company-sponsored phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)13
Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)1
Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)14
Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor versus fulvestrant plus a CDK 4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)15
Giredestrant plus Phesgo (pertuzumab, trastuzumab, and hyaluronidase subcutaneous) versus Phesgo in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)16
About oestrogen receptor (ER)-positive breast cancer
Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year.17 Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.18

ER-positive breast cancer accounts for approximately 70% of breast cancer cases.2 A defining feature of ER-positive breast cancer is that its tumour cells have receptors that attach to oestrogen, which can contribute to tumour growth.19

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity.3 Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy.3,20 There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

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.