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Nuvalent Highlights Recent Pipeline Progress, Reiterates Key Anticipated Milestones, and Reports Third Quarter 2025 Financial Results

On October 30, 2025 Nuvalent, Inc.(Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported pipeline progress, reiterated key anticipated milestones, and announced third quarter 2025 financial results.

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"The third quarter of 2025 marked the achievement of a significant milestone with the completion of our NDA submission for zidesamtinib in TKI pre-treated advanced ROS1-positive NSCLC. We look forward to working closely with the FDA throughout the review process, as well as continuing to engage with the agency on potential opportunities for line-agnostic expansion," said Darlene Noci, A.L.M., Chief Development Officer of Nuvalent. "We remain on track to share topline pivotal data this quarter from our ALKOVE-1 trial of neladalkib in TKI pre-treated advanced ALK-positive NSCLC, and continue to progress ALKAZAR, our global Phase 3 randomized, controlled trial of neladalkib for TKI-naïve patients with advanced ALK-positive NSCLC."

"Our commercial preparedness activities are well underway as we carry forward the momentum from these exciting development milestones and continue our efforts to transition toward becoming a fully integrated commercial-stage biopharmaceutical company," said Alex Balcom, Chief Financial Officer of Nuvalent. "Combined with a strong financial position with cash runway anticipated into 2028, we believe we are well positioned to achieve our goal of delivering a new and potential best-in-class option for all patients with ROS1 or ALK-positive NSCLC."

"We are also pleased to have recently shared the first report of preliminary clinical data demonstrating the potential for neladalkib to address medical needs for patients with ALK-positive solid tumors beyond NSCLC, and new preclinical data further demonstrating the potential for NVL-330 to offer a differentiated profile for HER2-altered NSCLC," said James Porter, Ph.D., Chief Executive Officer of Nuvalent. "With a portfolio anchored by complementary indications in biomarker-driven NSCLC and supported by a robust development and discovery pipeline, we continue to build towards our long-term vision of Nuvalent as a sustainable company capable of designing, developing and delivering precisely targeted therapies for patients with cancer."

Recent Pipeline Achievements and Anticipated Milestones

ROS1 Program

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The company has completed its rolling NDA submission for zidesamtinib in tyrosine kinase inhibitor (TKI) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC).

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Data supporting the NDA submission were presented in September as part of the Presidential Symposium at the IASLC 2025 World Conference on Lung Cancer.
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The company continues to engage with the FDA on potential opportunities for line-agnostic expansion.
ALK Program

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Evaluation of neladalkib is ongoing in the ALKOVE-1 Phase 1/2 trial for patients with advanced ALK-positive NSCLC and other solid tumors:
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The company presented preliminary data from the ongoing ALKOVE-1 Phase 1/2 clinical trial of neladalkib in patients with advanced ALK-positive solid tumors outside of NSCLC during a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025. Neladalkib demonstrated encouraging preliminary activity across a diverse set of advanced ALK-positive solid tumors, and was generally well-tolerated with a preliminary overall safety profile consistent with its ALK-selective, TRK sparing design, and with previously reported data.
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The company is on track to report topline pivotal data for TKI pre-treated patients with advanced ALK-positive NSCLC by year-end 2025.
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Enrollment is ongoing in ALKAZAR, the company’s global Phase 3 randomized, controlled trial designed to evaluate neladalkib for the treatment of patients with TKI-naïve ALK-positive NSCLC. Patients are randomized 1:1 to receive neladalkib or alectinib, a front-line standard of care, reflecting input from collaborating physician-scientists and alignment with global regulatory agencies.
HER2 Program

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Nuvalent presented new preclinical data for its novel HER2-selective inhibitor, NVL-330, at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), further supporting its potentially differentiated brain-penetrant profile. Compared to several currently available and investigational HER2 TKIs in the same preclinical assays, NVL-330 demonstrated a favorable efflux ratio and brain partitioning, metrics that are potentially positive predictors of brain exposure in humans. In preclinical models of intracranial activity, NVL-330 induced deep intracranial regression in mice. In the same models, the approved therapies T-DXd and zongertinib did not induce intracranial regression at their clinically relevant doses. Additionally, NVL-330 induced intracranial tumor regression in mice that had progressed in the CNS on zongertinib. These data add to the preclinical characterization of NVL-330 as a brain penetrant TKI that is broadly active against HER2 oncogenic alterations and selective over wild-type EGFR, and the company believes the data support its investigation in patients with advanced HER2-altered NSCLC.
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Enrollment is ongoing in the HEROEX-1 Phase 1a/1b clinical trial evaluating the overall safety and tolerability of NVL-330 for pre-treated patients with HER2-altered NSCLC. Additional objectives include determination of the recommended Phase 2 dose, characterization of NVL-330’s pharmacokinetic profile, and preliminary evaluation of anti-tumor activity. The company expects to continue to progress the HEROEX-1 trial throughout 2025.

Upcoming Events

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Jefferies 2025 Global Healthcare Conference in London: Management will be participating in a fireside chat on Wednesday, November 19, 2025, at 5:00 p.m. GMT. A live webcast will be available in the Investors section of Nuvalent’s website at www.nuvalent.com, and will be archived for 30 days following the conference.

Third Quarter 2025 Financial Results

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Cash Position: Cash, cash equivalents and marketable securities were $943.1 million as of September 30, 2025. Nuvalent continues to believe its existing cash, cash equivalents and marketable securities will be sufficient to fund its current operating plan into 2028.
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R&D Expenses: Research and development (R&D) expenses were $83.8 million for the third quarter of 2025.
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G&A Expenses: General and administrative (G&A) expenses were $28.9 million for the third quarter of 2025.
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Net Loss: Net loss was $122.4 million for the third quarter of 2025.

(Press release, Nuvalent, OCT 30, 2025, View Source [SID1234657162])

Nouscom to Present New Positive Phase 1b/2 Clinical and Translational Data on NOUS-209 Immunogenicity and Cancer Interception Potential in Lynch Syndrome Carriers at SITC 2025

On October 30, 2025 Nouscom, a clinical-stage biotech company developing next-generation neoantigen-targeted off-the-shelf and personalized cancer immunotherapies, reported it will give an oral late-breaker as well as a poster presentation of additional results from a Phase 1b/2 trial evaluating NOUS-209 in Lynch Syndrome (LS) carriers at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 40th Anniversary Annual Meeting being held in National Harbor, MD, USA on November 5-9, 2025. The company will also present further data validating NOUS-209 mechanism of action (MoA) in LS carriers at the SITC (Free SITC Whitepaper) meeting.

Oral Presentation Details:

Title: Final Ph1b/2 Results for NOUS-209 Monotherapy in Lynch Syndrome Carriers: Annual Revaccination Boosts T Cell Immunity Informing Future Cancer Interception Strategies

Session: Clinical Oral Abstract Session 2
Date & Time: Saturday, November 8, 2025, 1:45 PM – 3:00 PM ET
Location: Gaylord National Resort & Convention Center, Potomac Ballroom

Poster Presentations Details:

Poster #118 – NOUS-209 Mechanism of Action Validation
Title: NOUS-209 Enables Broad Targeting of Primary and Metachronous Tumors in Lynch Syndrome

Session: Poster Hall
Time: Saturday, November 8, 2025, 9:00 AM – 6:35 PM ET
Location: Prince George’s ABC

Poster #1336 – NOUS-209 Clinical Data
Title: Final Ph1b/2 Results for NOUS-209 Monotherapy in Lynch Syndrome Carriers

Session: Poster Hall
Time: Saturday, November 8, 2025, 9:00 AM – 6:35 PM ET
Location: Prince George’s ABC

All abstracts are available on the SITC (Free SITC Whitepaper) website View Source

LS is a common inherited condition caused by DNA repair gene mutations. It affects approximately 1 in 300 people, leading to a significantly increased lifetime cancer risk of up to 80%. While current LS disease management relies on frequent screenings or preventive surgery, cancer interception with NOUS-209 aims to train the immune system to recognize and eliminate cancerous cells before they fully develop, grow and spread.

NOUS-209 is an off-the-shelf immunotherapy designed to target tumors with specific genetic deficiencies known as mismatch repair deficiency (dMMR) and/or microsatellite instability (MSI). These tumors produce unique markers known as frameshift peptide (FSP) neoantigens, which serve as tumor-specific neoantigens. Because these FSPs are exclusively found in cancerous cells, they are readily recognizable by the immune system and therefore are ideal targets for immunotherapy. NOUS-209 encodes 209 unique FSP neoantigens shared across multiple MSI tumor types, enabling its potential to treat a broad range of MSI-associated cancers.

Following positive Type B and C meetings with the US Food and Drug Administration (FDA), Nouscom has a clear path forward for the advancement of NOUS-209 into a registration-enabling Phase 2/3 clinical study for cancer interception in LS carriers.

The clinical trial NCT05078866 was led by researchers at The University of Texas MD Anderson Cancer Center, in collaboration with the Cancer Prevention Clinical Trials Network (CP-CTNet) and sponsored by the National Cancer Institute (grant # UG1CA242609). The activities are coordinated by the iCAN-PREVENT consortium of MD Anderson Cancer Center.

(Press release, NousCom, OCT 30, 2025, View Source;utm_medium=rss&utm_campaign=nouscom-to-present-new-positive-phase-1b-2-clinical-and-translational-data-on-nous-209-immunogenicity-and-cancer-interception-potential-in-lynch-syndrome-carriers-at-sitc-2025 [SID1234657161])

Nkarta to Participate in November Investor Conferences

On October 30, 2025 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported its participation in the following investor conferences next month:

Stifel 2025 Healthcare Conference
November 12, 2025
10:40 a.m. ET – fireside chat

TD Cowen’s Immunology & Inflammation Summit
November 13, 2025
5 p.m. ET – fireside chat

A simultaneous webcast of the event will be available on the Investors section of Nkarta’s website, www.nkartatx.com, and a replay will be archived on the website for approximately 90 days.

(Press release, Nkarta, OCT 30, 2025, View Source [SID1234657160])

Moleculin to Highlight its Ongoing Phase 3 Acute Myeloid Leukemia “MIRACLE” Clinical Trial at the 14th Annual Acute Leukemia Meeting

On October 30, 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 cancers and viral infections, reported it will present at the 14th Annual Acute Leukemia Meeting being held October 30-31, 2025 at the MD Anderson Cancer Center Spain Foundation in Madrid, Spain.

Details of the presentation are as follows:

Title: L-Annamycin – Non-Cardiotoxic Anthracycline; MIRACLE Pivotal AML Study
Session: Lunch Session: Moleculin
Presenter: Dr. Paul Waymack, Senior Chief Medical Officer of Moleculin
Date and Time: Thursday, October 30th at 2:35 PM CEST

As part of the presentation, Dr. Waymack will discuss the Company’s ongoing pivotal Phase 2B/3, multi-center, randomized, double-blind, placebo-controlled, adaptive design study of Annamycin in combination with cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") for the treatment of adult patients with acute myeloid leukemia (AML) who are refractory to or relapsed (R/R) after induction therapy (R/R AML). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a global approval trial, including sites in the US, Europe and the Middle East (clinicaltrials.gov NCT06788756; euclinicaltrials.eu 2024-518359-47-00).

Annamycin, also known by its non-proprietary name of naxtarubicin, currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory AML, in addition to Orphan Drug Designation for the treatment of STS lung mets. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory AML from the EMA.

For more information about the 14th Annual Acute Leukemia Meeting, please visit the meeting website.

(Press release, Moleculin, OCT 30, 2025, View Source [SID1234657159])

Molecular Partners Reports Q3 2025 Financial Results and Clinical Progress, with DLL3-Targeting Radio-DARPin MP0712 Phase 1 Launch Expected in 2025

On October 30, 2025 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported corporate highlights and unaudited financial results for the third quarter of 2025.

"We are excited to present initial clinical imaging data this November on MP0712, the 1st Radio-DARPin targeting DLL3, from compassionate care use in South Africa. The IND application for MP0712 has been filed and we see the alpha-targeting approaches for DLL3 in lung cancer as a valuable new modality for patients. Building on that progress, we are establishing a pipeline of additional Radio-DARPins with our partner Orano Med for selected targets, including mesothelin for ovarian cancer," said Patrick Amstutz, Ph.D., CEO of Molecular Partners. "MP0533 is the first-ever tetraspecific T-cell engager to demonstrate safety and efficacy in AML. We will report additional data on optimized dosing and a deeper understanding on the ideal patient profile for MP0533. This understanding is important to plan next steps and is supportive of positioning of our drug in the treatment landscape."

Research & Development Highlights

MP0712 (212Pb x DLL3), Radio-DARPin Pipeline and Collaboration with Orano Med

The Phase 1 Investigational New Drug (IND) application for MP0712, a 212Pb-based Radio-DARPin therapy (RDT) candidate targeting the tumor-associated protein delta-like ligand 3 (DLL3), co-developed with Orano Med for the treatment of small cell lung cancer (SCLC) and other DLL3-expressing neuroendocrine cancers, has been filed. Dialogue with the FDA is ongoing and, pending regulatory clearance, the Phase 1 trial is expected to initiate before the end of 2025.

Molecular Partners presented preclinical data in April at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, showing high tumor uptake, promising efficacy and a favorable safety profile for MP0712 in mouse models matching clinically-relevant DLL3 expression levels.

In H1 2025, Molecular Partners accepted a request from the Nuclear Medicine Research Infrastructure (NuMeRI) in South Africa to provide MP0712 for imaging use under the legal framework in South Africa for compassionate care (also referred to as Section 21 of the Medicines and Related Substances Act). This approach enables the generation of initial images applying MP0712 labeled with 203Pb in patients with SCLC and other DLL3-expressing neuroendocrine cancers. As per courtesy of NuMeRI, the Company will present first images from the MP0712 compassionate care program at the Targeted Radiopharmaceuticals (TRP) Summit EU in November. The NuMeRI team, lead by Dr. Mike Sathekge, plans to report the full imaging and dosimetry data of MP0712 at the Theranostics World Conference (TWC) in January 2026.
203Pb and 212Pb are an element-equivalent pair of lead (Pb) isotopes, with 203Pb primarily used for imaging and 212Pb for therapeutic applications (targeted alpha therapy, TAT). As a "matched pair", pre-treatment imaging with 203Pb provides a prediction of treatment behavior with 212Pb.

In January 2025, Molecular Partners and Orano Med expanded their agreement to co-develop up to ten radiotherapy programs. In addition to its world class expertise and capabilities in the development of TAT with 212Pb, Orano Med will ensure the production of the 212Pb-based Radio-DARPins for clinical trials and commercialization. Orano Med possesses virtually unlimited source material for 212Pb production and has established robust and independent supply and manufacturing capabilities required for the seamless delivery of TAT to clinical sites internationally.

The second RDT program slated for clinical development is MP0726, targeting mesothelin (MSLN), a tumor target overexpressed across several cancers with high unmet need, such as ovarian cancer. Molecular Partners has developed Radio-DARPins able to selectively bind to membrane-bound MSLN without being impacted by shed MSLN, which has hampered the development of other MSLN-targeted therapeutics. The Company presented preclinical data on MP0726 at the 2025 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in June. The Company is planning to progress several programs in 2026, including MP0726.

MP0533 (Multispecific T Cell Engager; CD33 x CD123 x CD70 x CD3)

MP0533 is currently being evaluated in a Phase 1/2a clinical trial for relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/AML (NCT05673057). Molecular Partners presented updated data from the study at the 30th Annual European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June, with promising antitumor activity observed in cohort 8. Three of 8 (>30%) evaluable patients in this cohort achieved a clinical response after the first cycle, and two patients maintained their responses for over three months, including one patient still on treatment today (>12 months response duration). Cohort 8 benefited from a higher starting dose and a faster step-up dosing schedule, leading to improved exposure within the predicted therapeutic range and notable blast reduction in most patients, with an acceptable safety profile after dose adjustment.

Encouraged by these results, Molecular Partners amended the dosing scheme for cohorts 9 and 10 by further accelerating the step-up dosing, increasing the dosing frequency and introducing anti-CD20 premedication to achieve higher cumulative exposure as well as enhanced depth and duration of responses. Cohort 9 is exploring a lower target dose than cohort 8 to assess the safety of up to daily dosing in the first 14 days of treatment. Data from cohort 9 will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2025. Cohort 10, which aims at reaching the same target dose as cohort 8 while exposing patients to more drug over time, is now enrolling and dosing patients.

MP0533 continues to show broad activity in a mutation-agnostic manner, with initial blast reductions in a majority of patients treated, and an acceptable safety profile. The data continue to indicate that the patients more likely to see durable responses will be those who initiate therapy with a lower level of blasts at baseline. Molecular Partners plans to explore MP0533 in combination settings, both in patients with relapsed/refractory disease as well as in front-line setting, should favorable antitumor activity continue to be observed. Several consortia have approached Molecular Partners expressing interest in conducting such studies. The Company is engaging with key opinion leaders and regulators to discuss next steps.

MP0317 (Tumor-Localized Agonist; FAP x CD40)

Molecular Partners is supporting an investigator-initiated trial of MP0317, for which a study protocol has been approved (NCT07036380). This proof-of-concept randomized Phase 2 study, to be conducted by an expert network in France, is designed for the treatment of patients with advanced cholangiocarcinoma in combination with anti-PD-L1 therapy (durvalumab) and gemcitabine-cisplatin-based chemotherapy. The main objective of the study is to assess the 12-month progression free survival (PFS) in the experimental arm (N = 50 patients).

MP0317 is designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP), which is expressed in high amounts in the stroma of various solid tumors. The Company believes this tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies. Molecular Partners presented comprehensive biomarker analyses from the completed Phase 1 dose escalation trial of the localized CD40 agonist MP0317 in solid tumors at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in November 2024.

Switch-DARPins (Next-Generation Immune Cell Engagers)

By employing a multi-specific Switch-DARPin, Molecular Partners aims to increase the safety and potency of T cell engagers (TCEs). Preclinical proof-of-concept for a novel CD3 Switch-DARPin TCE with CD2 costimulation was presented at AACR (Free AACR Whitepaper) in April 2025. The data show the feasibility of conditional T cell activation with potent co-stimulation in solid tumors, but not in healthy tissues. In addition, data showed that the CD3 Switch-DARPin activates T cells specifically in the presence of cells co-expressing the tumor targets MSLN and EpCAM, thereby increasing tumor specificity. The Company will present an update on the CD3 Switch-DARPin program at SITC (Free SITC Whitepaper) in November 2025.

Corporate Governance Highlights

Molecular Partners appointed Martin Steegmaier, Ph.D., as Chief Scientific Officer (CSO) and member of its Executive Committee, effective October 1, 2025. Martin brings a wealth of experience in oncology drug development, having previously contributed to the advancement of several innovative cancer therapies at major biotech and pharmaceutical companies.

(Press release, Molecular Partners, OCT 30, 2025, View Source [SID1234657157])