On October 30, 2025 Bristol Myers Squibb (NYSE: BMY) reported results for the third quarter of 2025.

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"We delivered strong results this quarter as a result of continued execution across the business and ongoing Growth Portfolio momentum," said Christopher Boerner, Ph.D., board chair and chief executive officer, Bristol Myers Squibb. "We’re focused on building for the future by accelerating innovation, advancing our pipeline, staying agile and delivering more transformational medicines to more patients."

Third Quarter Results
$ in millions, except per share amounts 2025 2024 Change
Change Excl. FX**
Total Revenues $12,222 $11,892 3 % 2 %
Earnings/(Loss) Per Share – GAAP* 1.08 0.60 81 % N/A
Earnings/(Loss) Per Share – Non-GAAP* 1.63 1.80 (9) % N/A
Acquired IPRD Charges and Licensing Income Net Impact on Earnings/(Loss) Per Share (0.20) (0.09) N/A N/A

*GAAP and Non-GAAP earnings/(loss) per share include the net impact of Acquired IPRD charges and licensing income.
**See "Use of Non-GAAP Financial Information".

1

THIRD QUARTER RESULTS
All comparisons are made versus the same period in 2024 unless otherwise stated.
•Growth Portfolio revenues of $6.9 billion increased 18%, or 17% Ex-FX. Revenue growth was primarily driven by our immuno-oncology (IO) portfolio, Reblozyl, Camzyos and Breyanzi.
•Legacy Portfolio revenues of $5.4 billion decreased 12%, or 13% Ex-FX. Demand increased for Eliquis, which was more than offset by expected continued generic impact across the remainder of the Legacy Portfolio.
•Total revenues of $12.2 billion increased 3%, or 2% Ex-FX.
◦U.S. revenues of $8.3 billion increased 1%.
◦International revenues of $3.9 billion increased 6%, or 3% Ex-FX.
THIRD QUARTER PRODUCT REVENUE HIGHLIGHTS(d)

($ amounts in millions) Quarter Ended September 30, 2025
% Change from Quarter Ended September 30, 2024
% Change from Quarter Ended September 30, 2024 Ex-FX**

U.S.
Int’l
WW(c)
U.S.
Int’l
WW(c)
Int’l
WW(c)
Growth Portfolio
Opdivo $ 1,454 $ 1,077 $ 2,532 6 % 8 % 7 % 6 % 6 %
Opdivo Qvantig 60 7 67 N/A N/A N/A N/A N/A
Orencia 721 243 964 2 % 6 % 3 % 3 % 2 %
Yervoy 455 284 739 14 % 17 % 15 % 13 % 14 %
Reblozyl 494 121 615 38 % 35 % 37 % 31 % 37 %
Opdualag 259 40 299 20 % 122 % 28 % 115 % 27 %
Breyanzi 251 109 359 45 % 115 % 60 % 104 % 58 %
Camzyos 238 57 296 76 % 177 % 89 % 168 % 88 %
Zeposia 113 48 161 8 % 13 % 9 % 6 % 7 %
Abecma 51 86 137 (34) % 80 % 9 % 71 % 6 %
Sotyktu 51 29 80 — % 91 % 21 % 87 % 20 %
Krazati 48 5 53 52 % 144 % 58 % 133 % 57 %
Cobenfy 43 — 43 N/A N/A N/A N/A N/A
Other Growth Products(a)
195 319 514 8 % 22 % 16 % 21 % 16 %
Total Growth Portfolio
4,432 2,425 6,857 17 % 20 % 18 % 17 % 17 %
Legacy Portfolio
Eliquis 2,631 1,115 3,746 29 % 16 % 25 % 11 % 23 %
Revlimid 485 89 575 (60) % (55) % (59) % (56) % (59) %
Pomalyst/Imnovid 596 79 675 (15) % (61) % (25) % (61) % (25) %
Sprycel 69 49 119 (69) % (24) % (59) % (25) % (59) %
Abraxane 24 50 74 (84) % (50) % (71) % (49) % (70) %
Other Legacy Products(b)
92 85 177 (11) % (29) % (21) % (30) % (21) %
Total Legacy Portfolio 3,897 1,468 5,365 (12) % (11) % (12) % (14) % (13) %
Total Revenues $ 8,329 $ 3,893 $ 12,222 1 % 6 % 3 % 3 % 2 %

** See "Use of Non-GAAP Financial Information".
(a) Includes Augtyro, Onureg, Inrebic, Nulojix, Empliciti and royalty revenues.
(b) Includes other mature brands.
(c) Worldwide (WW) includes U.S. and International (Int’l).
(d) For the above table and all subsequent tables, certain totals may not sum due to rounding. Percentages have been calculated using unrounded amounts.

2

THIRD QUARTER COST & EXPENSES
All comparisons are made versus the same period in 2024 unless otherwise stated.
The table below presents selected line-item information.

Three Months Ended September 30, 2025 Three Months Ended September 30, 2024
($ amounts in millions)
GAAP
Specified Items**
Non-GAAP
GAAP
Specified Items**
Non-GAAP
Cost of products sold
$ 3,435 (122) $ 3,312 $ 2,957 (101) $ 2,856
Gross margin(a)
71.9 % 72.9 % 75.1 % 76.0 %
Selling, general and administrative
1,789 (1) 1,788 1,983 (7) 1,976
Research and development
2,528 (95) 2,433 2,374 (21) 2,353
Acquired IPRD
633 — 633 262 — 262
Amortization of acquired intangible assets
831 (831) — 2,406 (2,406) —
Other (income)/expense, net
(108) (98) (206) 234 (275) (41)
Effective tax rate
29.5 % (7.2) % 22.3 % 27.5 % (9.0) % 18.5 %

**See "Use of Non-GAAP Financial Information" and refer to the Specified Items schedule below for further detail.
(a) Represents revenue minus cost of products sold divided by revenue.

•Gross margin on a GAAP and non-GAAP basis was 71.9% and 72.9% in 2025, and 75.1% and 76.0% in 2024, respectively, reflecting the change in product mix.
•Selling, general and administrative expenses of $1.8 billion decreased 10% on a GAAP and non-GAAP basis, primarily driven by our ongoing strategic productivity initiative.
•Research and development expenses of $2.5 billion increased 6% on a GAAP basis, primarily due to an IPRD impairment charge. Non-GAAP research and development expenses of $2.4 billion increased 3%, primarily due to the impact of recent acquisitions, partially offset by our ongoing strategic productivity initiative.
•Acquired IPRD charges of $633 million increased from $262 million on a GAAP and non-GAAP basis, primarily driven by the Philochem licensing arrangement and achievement of a milestone under the SystImmune collaboration. Licensing income increased from $25 million to $107 million on a GAAP and non-GAAP basis, primarily reflecting the execution of an out-licensing arrangement in 2025.
•Amortization of acquired intangible assets of $831 million decreased 65% on a GAAP basis, primarily due to lower amortization expense related to Revlimid.
•Effective tax rate increased from 27.5% to 29.5% on a GAAP basis, and from 18.5% to 22.3% on a non-GAAP basis. The increase in the non-GAAP effective tax rate was driven by jurisdictional earnings mix.
•Net income attributable to Bristol Myers Squibb of $2.2 billion, or $1.08 per share, increased from $1.2 billion, or $0.60 per share, on a GAAP basis. On a non-GAAP basis, net income attributable to Bristol Myers Squibb of $3.3 billion, or $1.63 per share, decreased from $3.7 billion, or $1.80 per share. GAAP and non-GAAP EPS include the impacts of Acquired IPRD charges and licensing income.

PRODUCT AND PIPELINE UPDATES
Entries organized by date and inclusive of third quarter and recent updates.
Asset(s)
Date Announced
Milestone
Sotyktu (deucravacitinib)
October 27
52-week data from the pivotal Phase 3 POETYK PsA-1 trial demonstrated that Sotyktu improved and maintained meaningful clinical responses, inhibition of radiographic progression and patient-reported outcomes in adults with active psoriatic arthritis.

In addition, data from an integrated analysis of the Phase 2 PAISLEY-SLE and PAISLEY long-term extension studies supported the safety and efficacy with up to four years of Sotyktu treatment for moderate-to-severe systemic lupus erythematosus (SLE).
CD19 NEX-T (BMS-986353)
October 25
Announced positive, updated data and early results from the Phase 1 Breakfree-1 study evaluating BMS-986353, an investigational, autologous CD19-targeted NEX-T CAR T cell therapy, across the systemic sclerosis, SLE and idiopathic inflammatory myopathies cohorts. The preliminary Phase 1 safety and efficacy results are consistent with the potential for immune reset, showing robust CAR T cell expansion, complete B cell depletion and re-emergence of a naive B cell phenotype across all three cohorts.
izalontamab brengitecan
(iza-bren)
October 17
First disclosure of safety and efficacy data presented with SystImmune from the global Phase I US-Lung-101 study of iza-bren, a potentially first-in-class EGFR x HER3 bispecific antibody-drug conjugate, demonstrated promising antitumor activity in heavily pre-treated patients across multiple tumor types, as well as a manageable safety profile.
BMS-986446 October 1
The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BMS-986446, a potential best-in-class, anti-microtubule binding region-tau antibody currently in Phase 2 development for the treatment of early Alzheimer’s disease.
Sotyktu September 25
Announced an expansion of the company’s direct-to-patient offerings, providing eligible U.S. patients with steeply discounted prices for Sotyktu via the new BMS Patient Connect platform, beginning January 2026.
iberdomide September 23
The Phase 3 EXCALIBER-RRMM study evaluating iberdomide, an investigational cereblon E3 ligase modulator (CELMoD), combined with standard therapies (daratumumab + dexamethasone) in patients with relapsed or refractory multiple myeloma demonstrated a statistically significant improvement in minimal residual disease (MRD) negativity rates, compared with the control arm, in a planned interim analysis of the MRD endpoint.
pumitamig (BNT327 / BMS-986545)
September 8
First disclosure of data presented with BioNTech SE from the global randomized Phase 2 trial (NCT06449209) evaluating pumitamig, an investigational bispecific antibody targeting PD-L1 x VEGF-A, plus chemotherapy in patients with extensive-stage small cell lung cancer demonstrated encouraging anti-tumor responses with a positive trend in the secondary endpoint of progression free survival.

Additionally, this week pivotal studies for pumitamig and chemotherapy combinations are now initiating in first-line (1L) microsatellite stable colorectal cancer and 1L gastric cancer.
Camzyos (mavacamten)
August 29
Results from the global, retrospective COLLIGO-HCM study showed that Camzyos was associated with reductions in left ventricular outflow tract obstruction and improvements in symptom burden in a racially diverse population of patients with symptomatic obstructive hypertrophic cardiomyopathy treated in an international, real-world setting.

iza-bren
August 18
The FDA granted Breakthrough Therapy Designation to iza-bren for the treatment of locally advanced or metastatic non-small cell lung cancer with epidermal growth factor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor and platinum-based chemotherapy.
Breyanzi (lisocabtagene maraleucel)
August 4
The FDA accepted the supplemental biologics license application for Breyanzi as a potential treatment for adult patients with relapsed or refractory marginal zone lymphoma who have received at least two prior lines of systemic therapy. The FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act goal date of December 5, 2025.

Business Development
In October 2025, the company announced a definitive agreement to acquire Orbital Therapeutics. The acquisition includes OTX-201, Orbital’s lead RNA immunotherapy preclinical candidate currently in IND-enabling studies. This investigational, next-generation CAR T-cell therapy is designed to reprogram cells in vivo and has the potential to offer a best-in-class profile for treating autoimmune diseases, aligned with Bristol Myers Squibb’s overall immune reset strategy. This in vivo approach, in which the patient’s own body serves as the manufacturer of CAR T-cells, has the potential to offer a reduced treatment burden, added convenience and improved accessibility compared to ex vivo CAR T-cell therapies. Bristol Myers Squibb will also gain access to Orbital’s differentiated RNA technology platform that integrates advanced RNA engineering and delivery methods, offering the potential to expand therapeutic applications and address additional diseases. The transaction is subject to the satisfaction of customary closing conditions.

Financial Guidance
Bristol Myers Squibb is increasing its full-year 2025 non-GAAP revenue guidance from a range of approximately $46.5 billion to $47.5 billion, to a range of approximately $47.5 billion to $48.0 billion. This update primarily reflects the continued strong performance of our Growth Portfolio.
Full-year other income and expense in 2025 is now expected to be approximately $500 million of income due to higher-than-anticipated royalties and licensing income, as well as favorable interest income.
Non-GAAP EPS is now expected to be in the range of $6.40 – $6.60, inclusive of an $(0.80) per share net impact related to Acquired IPRD charges and licensing income.
Non-GAAP2,3

July
(Prior) October
(Updated)
Total Revenues
(Reported & Ex-FX)
~$46.5 – $47.5 billion ~$47.5 – $48.0 billion
Gross Margin % ~72% No change
Operating Expenses1
~$16.5 billion No change
Other income/(expense) ~$250 million ~$500 million
Effective tax rate ~18% No change
Diluted EPS $6.35 – $6.65 $6.40 – $6.60
Acquired IPRD Charges and Licensing Income Included in Diluted EPS $(0.60) $(0.80)

1 Operating Expenses = SG&A and R&D.
2 See "Use of Non-GAAP Financial Information."
3 July was calculated using foreign exchange rates as of July 25, 2025, and October was calculated using foreign
exchange rates as of October 28, 2025.

The 2025 financial guidance excludes the impact of any potential future strategic acquisitions, including Orbital Therapeutics, which is expected to close in the fourth quarter of 2025, divestitures, specified items that have not yet been identified and quantified, and the impact of future Acquired IPRD charges and licensing income. To the extent we have quantified the impact of significant R&D charges or other income resulting from upfront or contingent milestone payments in connection with asset acquisitions or licensing of third-party intellectual property rights, we may update this information from time to time on our website, www.bms.com, in the "Investors" section. Non-GAAP guidance assumes exchange rates as of the date noted. The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

(Press release, Bristol-Myers Squibb, OCT 30, 2025, View Source [SID1234657142])

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.

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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])

On October 30, 2025 Parabilis Medicines, a clinical-stage biopharmaceutical company committed to creating extraordinary medicines for people living with cancer, reported preliminary clinical and preclinical findings across its Helicon peptide pipeline 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) in Boston, Massachusetts.

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The findings reinforce the broad potential of FOG-001, the company’s lead investigational therapy and the first-ever direct Wnt/β-catenin:TCF inhibitor, to act across a range of rare and more prevalent solid tumors linked by the same dysregulated biology of the Wnt/β-catenin pathway. Single-agent activity resulting in tumor shrinkage by at least 30% (partial response (PR)) was observed in five low-complexity tumor types, with strong scientific support as well for FOG-001’s potential in combination therapy for more complex tumors, including microsatellite-stable colorectal cancer (MSS CRC).

Together with positive preclinical read-outs demonstrating pharmacologic proof of concept for the company’s discovery-stage Helicon peptides in prostate cancer targeting the ERG and active androgen receptor (ARON) targets, these data highlight how the company’s Helicon platform can repeatably target high-impact "undruggable" targets long considered inaccessible to conventional therapeutic approaches.

"Just one week after presenting the first clinical proof that β-catenin:TCF can be drugged, we are showing the breadth of what this breakthrough could mean for science and for patients," said Mathai Mammen, M.D., Ph.D., Chairman and CEO of Parabilis Medicines. "FOG-001 is demonstrating meaningful signs of clinical activity across multiple Wnt/β-catenin-driven tumors, supporting its continued development in both simpler and more biologically complex Wnt-driven cancers through both monotherapy and combination therapy approaches."

He added, "Together with our preclinical advances in prostate cancer, the data illustrate the potential of Helicons to take on some of the toughest problems in oncology and bring forward transformative medicines that could meaningfully improve outcomes for patients."

FOG-001 Clinical and Preclinical Findings

The Wnt/β-catenin pathway — first identified as a key cancer driver over 30 years ago — is implicated in millions of cancer cases annually, spanning many rare and prevalent solid tumors as well as diseases like familial adenomatous polyposis (FAP) that predispose individuals to certain cancers, including colorectal cancer and desmoid tumors. Despite its central role in cancer biology, the pathway’s critical β-catenin:TCF transcription complex has long been considered "undruggable."

Preliminary data from the ongoing Phase 1/2 trial of FOG-001 (NCT05919264), as of mid-August 2025, show that the therapy is well tolerated with no Grade 4/5 treatment-related adverse events or discontinuations and exhibits a favorable pharmacokinetic profile. As of this early data cut, an objective response rate (ORR) of 43% and a disease control rate (DCR) of 83%, per RECIST 1.1, were observed in non-CRC patients with Wnt pathway activating mutations (WPAM). Evidence of single-agent activity was observed across numerous Wnt/β-catenin–driven tumors, particularly in those with low mutational burden, including desmoid, adamantinomatous craniopharyngioma (ACP), ameloblastoma, salivary gland cancer, and solid pseudopapillary neoplasm (SPN).

In MSS CRC, a 50% DCR was achieved within the efficacious monotherapy dose range, with molecular data confirming on-target pathway inhibition and reprogramming of the tumor microenvironment toward a more immune-active state. Complementary preclinical studies demonstrated that FOG-001 enhances the effects of standard and emerging therapies for MSS CRC—showing in these preclinical models additive or synergistic activity with each of 5-fluorouracil and anti-VEGF regimens, synergy with anti–PD-1 therapy, and combination benefit with pan-RAS and KRAS G12D inhibitors.

Together, these findings highlight FOG-001’s broad pipeline potential — warranting continued development in Wnt pathway–activated low-complexity tumors, and as a backbone for rational combination regimens in more complex cancers. The Phase 1/2 study remains ongoing across a wide range of Wnt-driven rare and common cancers, with additional data readouts expected over the coming months.

Prostate cancer pipeline expansion

Parabilis also presented preclinical data advancing its prostate cancer franchise, focused on two long-standing oncogenic drivers that currently lack effective therapies. ERG-degrading Helicon peptides potently and durably reduced ERG protein levels —overexpressed in 40–50% of prostate cancers — showing in vivo pharmacologic proof-of-concept demonstrating tumor growth inhibition and efficacy comparable to or exceeding standard of care in challenging prostate cancer models.

In parallel, allosteric ARON Helicon degraders that bind a conserved site distinct from the androgen ligand pocket, were designed to selectively target the active, agonist-bound androgen receptor. These Helicon degraders block proliferation in AR-amplified prostate cancer cells, offering a strategy to overcome resistance driven by AR mutations or amplification. Importantly, this approach also allows for effective combinations with approved and emerging treatments that target the testosterone ligand pocket. Together, these data demonstrate the repeatability of the Helicon platform in addressing high-value, historically undruggable targets in oncology.

"Our Helicons are delivering against three of the most challenging and compelling targets in oncology, from β-catenin:TCF to ERG to ARON," said Fawzi Benzaghou, M.D., Chief Medical Officer of Parabilis Medicines. "By pursuing bold science that makes the undruggable druggable, we’re opening new therapeutic possibilities for patients with few or no options. These data reinforce the power of our α-helical peptide platform to repeatedly unlock difficult targets and advance medicines with the potential for extraordinary patient impact."

About the Phase 1/2 trial of FOG-001
FOG-001 is being evaluated in a first-in-human Phase 1/2 multicenter, open-label study (NCT05919264) assessing its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity. The trial includes dose-escalation and dose-expansion phases and is testing FOG-001 both as a monotherapy and in combination with other anticancer agents in patients with advanced or metastatic solid tumors likely or known to harbor a Wnt pathway–activating mutation (WPAM).

About FOG-001
FOG-001 is an investigational first-in-class competitive inhibitor of β-catenin interactions with the T-cell factor (TCF) family of transcription factors and is currently in clinical development. By directly targeting the β-catenin:TCF protein-protein interaction, FOG-001 is intended to block the Wnt signaling pathway irrespective of the various APC and β-catenin mutations that typically drive disease.

FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the key downstream node, disrupting the interaction between β-catenin and the TCF transcription factors, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis.

FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors.

(Press release, Parabilis Medicines, OCT 30, 2025, View Source [SID1234657179])

On October 30, 2025 Calidi Biotherapeutics, Inc. (NYSE American: CLDI) ("Calidi" or the "Company"), a clinical-stage biotechnology company pioneering the development of systemically delivered, targeted genetic medicines, reported the presentation of new data on its first therapeutic candidate from its RedTail platform, CLD-401, at the Society of Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) Annual Meeting.

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CLD-401 is a tumor-tropic oncolytic virus designed to home to metastatic sites after systemic administration, replicate only in tumors cells, induce an immune priming event at the tumor site, and express high levels of IL-15 superagonist, a potent cytokine that induces NK and T-cell responses to the tumor, in the tumor microenvironment (TME).

"The RedTail platform represents a major advance in virotherapy and genetic medicines," said Antonio F. Santidrian, PhD, Chief Scientific Officer and Head of Technical Operations at Calidi. "RedTail allows for systemically administered genetic medicines that avoid immune clearance, are tropic for tumor cells, induce tumor lysis and immunologically prime the TME, and can deliver a genetic payload."

"In our syngeneic models, CLD-401 can reach metastatic sites when administered systemically where it can destroy tumor cells through a novel mechanism that also induces an immune priming effect," added Eric Poma, PhD, Chief Executive Officer. "CLD-401 builds on these mechanisms by also delivering high levels of IL-15 superagonist to the TME to activate a potent T-cell and NK cell response to the tumor."

Calidi is currently conducting IND-enabling studies for CLD-401 and anticipates submitting an Investigational New Drug (IND) application by the end of 2026. The company is also actively pursuing strategic partnerships to accelerate clinical development and broaden the impact of its RedTail platform.

CLD-401 Presentation

Meeting: SITC (Free SITC Whitepaper) 40th Anniversary Annual Meeting, November 7–9, 2025, National Harbor, MD
Title: In Situ Tumor Delivery of IL-15 Superagonist via RedTail Gene Therapy Achieves Durable Tumor Clearance
Abstract Number: 1175
Presentation Time: Friday, November 7, 2025, 12:15–1:45 PM and 5:35–7:00 PM

(Press release, Calidi Biotherapeutics, OCT 30, 2025, View Source [SID1234657145])

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])