On November 17, 2025 Nuvalent, Inc. (the "Company") reported positive topline pivotal data for neladalkib, an investigational ALK-selective inhibitor, in tyrosine kinase inhibitor ("TKI") pre-treated patients with advanced ALK-positive non-small cell lung cancer ("NSCLC") from the global ALKOVE-1 Phase 1/2 clinical trial. Additionally, the Company shared the first report of preliminary data from the Phase 2 exploratory cohort for TKI-naïve patients with advanced ALK-positive NSCLC from the ALKOVE-1 study.

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Summary of Topline Pivotal Data

Neladalkib is being evaluated in ALKOVE-1, a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors. The recommended Phase 2 dose ("RP2D") for neladalkib of 150 mg once daily ("QD") was determined during the Phase 1 dose-escalation portion of the trial. The global, single-arm, multi-cohort, open-label Phase 2 portion is designed to evaluate neladalkib at the RP2D with registrational intent for TKI pre-treated patients with advanced ALK-positive NSCLC. Global enrollment in ALKOVE-1 remains ongoing for adult and adolescent patients with ALK-positive solid tumors other than NSCLC, and for adolescent patients with ALK-positive NSCLC.

In this topline pivotal dataset for the TKI pre-treated ALK-positive NSCLC population, data are pooled across Phase 1 and 2 and reported for the primary objective of objective response rate (ORR, RECIST 1.1) by blinded independent central review ("BICR"). Key secondary objectives include duration of response ("DOR"), intracranial ORR ("IC-ORR"), and safety.

As of the data cut-off date of August 29, 2025, 781 patients with ALK-positive solid tumors had received neladalkib at any starting dose across the Phase 1 and Phase 2 portions of the ALKOVE-1 clinical trial. Of these, 656 patients with advanced ALK-positive NSCLC were treated with neladalkib at the RP2D.

Efficacy Analysis in TKI Pre-treated Advanced ALK-positive NSCLC

The pivotal primary analysis population consisted of 253 TKI pre-treated patients with advanced ALK-positive NSCLC with measurable disease by BICR who received neladalkib at the RP2D by September 30, 2024, with DOR follow-up of at least 6 months available for nearly all responders.

The pivotal primary analysis population was distinct from the ALK TKI pre-treated populations that have been reported for the currently available ALK TKIs:

•
Patients received a median of 3 prior lines of therapy (range, 1 – 11) and 51% had received prior chemotherapy.

•
78% of patients had received 2 or more prior ALK TKIs ± prior chemotherapy, of which 91% had received prior lorlatinib. No approved therapies have demonstrated activity after lorlatinib.

•
19% of patients had a secondary ALK G1202R resistance mutation, and 17% had a compound ALK resistance mutation, which are key drivers of disease progression.

•
40% of patients had active CNS disease by BICR at baseline.

Of the overall TKI pre-treated population, 25% (63/253) of patients were lorlatinib-naïve. Within this subpopulation:

•
25% received prior chemotherapy.

•
100% had received ≥ 1 prior 2G ALK TKI ± prior chemotherapy, of which 70% received prior alectinib only. No patients received crizotinib as their only ALK TKI.

•
19% of patients had a secondary ALK G1202R mutation.

•
35% had active CNS disease by BICR at baseline.

Activity was observed across subsets of TKI pre-treated patients, and durability of response was assessed as the probability of patients remaining in response for at least 6, 12, and 18 months by Kaplan-Meier estimate (Table 1).

Table 1. Any prior ALK TKI
± chemotherapy a
TKI Pre-treated,

Lorlatinib-naïve b

n

253 63
ORR, % (n/N)

(95% CI)

31% (79/253) c, d

(26, 37)

46% (29/63) e

(33, 59)

% DOR ≥ 6 months f

(95% CI)

76%

(64, 84)

89%

(69, 96)

% DOR ≥ 12 months f

(95% CI)

64%

(51, 75)

80%

(58, 91)

% DOR ≥ 18 months f

(95% CI)

53%

(34, 68)

60%

(19, 85)

G1202R mutation g

n

47 12
ORR, % (n/N)

(95% CI)

68% (32/47) h, i

(53, 81)

83% (10/12)

(52, 98)

% DOR ≥ 6 months f

(95% CI)

84%

(65, 93)

90%

(47, 99)

% DOR ≥ 12 months f

(95% CI)

80%

(61, 91)

77%

(34, 94)

% DOR ≥ 18 months f

(95% CI)

70%

(42, 86)

77%

(34, 94)

Measurable CNS lesions

n

92 j 24 k
IC-ORR, % (n/N)

(95% CI)

32% (29/92) l, m

(22, 42)

63% (15/24) l

(41, 81)

IC-CR, % (n/N)

13% (12/92) n 21% (5/24) n
% IC-DOR ≥ 6 months f

(95% CI)

81%

(59, 91)

92%

(57, 99)

% IC-DOR ≥ 12 months f

(95% CI)

71%

(48, 85)

92%

(57, 99)

% IC-DOR ≥ 18 months f

(95% CI)

71%

(48, 85)

92%

(57, 99)

a Median DOR ("mDOR") not reached with median follow-up of 11.3 months.

b mDOR not reached.

c Includes 2 unconfirmed partial responses ("uPRs").

d Includes responses in patients previously treated with lorlatinib (ORR = 26% [50/190 including 2 uPRs] with mDOR = 17.6 months [95% CI: 6.9, NE]).

e For patients receiving only 1 prior 2nd generation ALK TKI (alectinib [n = 44] or brigatinib [n = 2]) ± chemotherapy, ORR was 48% (22/46) with mDOR not reached, and DOR ≥ 12 and 18 months of 74% (95% CI: 48, 88).

f Estimated for responders by Kaplan-Meier analysis.

g ALK G1202R mutation identified in local or central testing of blood ("ctDNA") or tissue. Patients may have had other mutations in addition to ALK G1202R.

h Includes responses in patients with compound ALK mutations (≥2 ALK mutations, cis allelic configuration not determined in all cases) after ≥ 2 prior ALK TKIs (ORR = 58% [25/43, including 1 uPR] with DOR ≥ 12 months of 69% [95% CI: 45, 84]) and in patients with ALK resistance mutations other than G1202R, including C1156Y, I1171N, I1171T, F1174C, F1174L, V1180L, L1196M, L1198F, D1203N, E1210K, and G1269A.

i Includes 1 uPR.

j For intracranial ("IC") responders, the emerging IC-mDOR was 21.6 months (95% CI: 10.1, NE) and continues to mature.

k For IC-responders, the emerging IC-mDOR was 21.6 months (95% CI: 21.6, NE) and continues to mature.

l Includes 2 IC-uPRs.

m IC responses were also observed in lorlatinib-experienced patients with measurable CNS lesions at baseline (IC-ORR = 21%, 14/68) with IC-mDOR not reached, IC-DOR ≥ 6 months of 71% (95% CI: 41, 88), and IC-DOR ≥ 12 and 18 months of 55% (95% CI: 26, 77).

n Includes 1 IC-uCR with prior confirmed IC-PR.

Preliminary Data from Exploratory Cohort for TKI-Naïve Patients with Advanced ALK-positive NSCLC

Encouraging preliminary data were available for 44 TKI-naïve patients with advanced ALK-positive NSCLC and measurable disease by BICR. These patients were treated with neladalkib at RP2D in an exploratory cohort of ALKOVE-1, with data cut-off of August 29, 2025. Patients may have received up to one prior line of chemotherapy.

The preliminary ORR was 86% (38/44; 2 uPRs) and a CR rate of 9% (4/44; 1 uCR with prior confirmed PR) was observed. DOR ranged from 1.7+ to 14.8+ months with DOR ≥ 6 and 12 months of 91% (95% CI: 70, 98) and only two progression events among responders. In 9 patients with measurable intracranial lesions, the IC-ORR was 78% (7/9) and the intracranial CR rate was 44% (4/9; 1 IC-uCR with prior confirmed IC-PR). The IC-DOR ranged from 3.1+ to 7.0+ months with no CNS progression among responders.

Global enrollment of TKI-naïve patients is ongoing in ALKAZAR, the Company’s Phase 3 randomized controlled trial of neladalkib versus alectinib.

Safety Analyses in Advanced ALK-positive NSCLC

Neladalkib demonstrated a generally well-tolerated safety profile consistent with its ALK-selective, TRK-sparing design.

In the 656 patients with advanced ALK-positive NSCLC treated at RP2D as of the data cut-off date, the median duration of exposure was 6.0 months (range, 0.1, 28.4). The most frequent treatment-emergent adverse events ("TEAEs") occurring in ≥ 15% of patients were alanine aminotransferase increased (47%), aspartate aminotransferase increased (44%), constipation (28%), dysgeusia (23%), peripheral edema (18%), cough and nausea (16% each).

The most common TEAE of transaminase elevations were generally observed to be asymptomatic lab abnormalities that were low-grade, transient, and reversible with dose interruptions or reductions. Preliminary data suggest increased incidence in less heavily pre-treated patients. Enhanced monitoring for transaminase elevations and prompt dose interventions have been implemented in the protocol for the ALKAZAR Phase 3 randomized, controlled trial.

Across the 656 patients treated in ALKOVE-1 at RP2D, dose reductions due to TEAEs occurred in 17% of patients and 5% of patients discontinued treatment due to TEAEs.

The Company plans to discuss the topline pivotal data for TKI pre-treated ALK-positive NSCLC with the U.S. Food and Drug Administration (the "FDA") at a pre-New Drug Application ("NDA") meeting. Additionally, the Company plans to present detailed study results at a future medical meeting.

(Press release, Nuvalent, NOV 17, 2025, View Source [SID1234660025])

On November 17, 2025 Solve Therapeutics, a clinical-stage biotechnology company developing best-in-class antibody-drug conjugates (ADCs) for solid tumor malignancies, reported it has raised $120 million in an oversubscribed and upsized financing to accelerate the development of its clinical pipeline and proprietary CloakLink linker platform.

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The round was led by Yosemite, with participation from Abingworth, Ally Bridge Group, B Capital, Balyasny Asset Management, Merck & Co., and SymBiosis, and existing investors Alexandria Venture Investments, AyurMaya Capital Management, DC Global Ventures, General Atlantic, and Surveyor Capital (a Citadel company). This latest funding follows a $75 million financing completed in December 2024, bringing Solve’s total capital raised to $321 million.

Solve Therapeutics was founded to develop next-generation ADCs capable of addressing unique challenges presented by solid tumors. Traditional ADCs often face limitations related to payload hydrophobicity, including sub-optimal pharmacokinetics and plasma stability, which can compromise safety and efficacy.

Solve’s proprietary CloakLink technology was engineered to overcome these barriers by increasing ADC stability and decreasing ADC hydrophobicity across a broad range of drug-to-antibody ratios. The result is a class of ADCs with improved pharmacokinetics, enhanced plasma stability, and reduced toxicity, enabling improved therapeutic indices and overall performance.

The company’s lead programs, SLV-154 and SLV-324, are currently in Phase 1 clinical trials in patients with solid tumors. Both utilize the CloakLink platform and targeting antibodies that are specifically engineered for superior ADC performance. The ADCs are paired with novel diagnostic approaches to enable precision patient selection. The new funding will support the completion of Phase 1b studies for both programs and expand the company’s operational capabilities as it advances toward later-stage clinical development.

"We’re thrilled to partner with an outstanding syndicate of investors who share our vision for developing best-in-class ADCs," said Dave Johnson, CEO & Co-Founder, Solve Therapeutics. "Since founding the company, we’ve built a differentiated platform that combines next-generation ADC engineering, a superior hydrophilic linker system, and novel patient-selection diagnostics. This investment syndicate represents a strong endorsement of our science, our team, and our mission to develop more effective and safer targeted therapies for patients with solid tumors."

"Solve is the next wave of ADC innovation," said Dan McHugh, Investor at Yosemite and Solve Therapeutics board member. "By integrating therapeutic development with a novel diagnostic platform, Solve is pushing the boundaries of precision oncology and enabling a more personalized, effective approach to cancer care. Yosemite is excited to support the excellence and innovation demonstrated by this best-in-class team."

Founded by leaders behind VelosBio (acquired by Merck) and Acerta Pharma (acquired by AstraZeneca), Solve Therapeutics is applying decades of combined oncology and ADC expertise to build a pipeline of pioneering therapeutics and diagnostics targeting solid tumors with high unmet need.

(Press release, Solve Therapeutics, NOV 17, 2025, View Source [SID1234660041])

On November 17, 2025 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported that interim data from Cohort A of the ongoing Phase 2 open-label ADVANCED-2 trial of TARA-002 in BCG-Naïve patients with non-muscle invasive bladder cancer (NMIBC) will be featured during a poster session at the upcoming 26th Annual Meeting of the Society of Urologic Oncology (SUO) taking place from December 2, 2025 to December 5, 2025, in Phoenix, Arizona. The presentation will include data featured in the abstract published on the SUO website, as well as updated safety and efficacy data from 31 enrolled BCG-Naïve patients, the majority of whom have reached the six-month evaluation time point.

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ADVANCED-2 (NCT05951179) is a Phase 2 open-label trial assessing intravesical TARA-002 in NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive (n≈100) or BCG-Naïve (n=31). Trial subjects received an induction course, with or without a reinduction, of six weekly intravesical instillations of TARA-002, followed by a maintenance course of three weekly instillations every three months.

Details of the poster presentation are as follows:

Title: ADVANCED-2: Preliminary Efficacy and Safety Data in BCG-Naïve Participants with High-Grade Non-Muscle Invasive Bladder Cancer
Poster Number: 149
Poster Category: NMIBC
Session Title: Bladder Cancer
Session Date and Time: Thursday, December 4, 2025, 2:30 p.m. – 3:30 p.m. CT

About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma IL-6, IL-10, IL-12. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the sixth most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

(Press release, Protara Therapeutics, NOV 17, 2025, View Source [SID1234660026])

On November 17, 2025 Johnson & Johnson (NYSE: JNJ) reported that it has entered into a definitive agreement to acquire Halda Therapeutics OpCo, Inc. (Halda), a clinical-stage biotechnology company with a proprietary Regulated Induced Proximity TArgeting Chimera (RIPTAC) platform to develop oral, targeted therapies for multiple types of solid tumors, including prostate cancer, for $3.05 billion in cash. The transaction is expected to close within the next few months, subject to antitrust clearance and other customary closing conditions.

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The lead candidate, HLD-0915, is a clinical-stage therapy for prostate cancer, of which new diagnoses are projected to reach 1.7 million globally by 20301. Given the existing unmet need, this once-daily therapy has the potential to transform patient outcomes with its novel precision cancer cell-killing approach that can overcome mechanisms of resistance to treatment. The acquisition also includes several earlier candidates for breast, lung and multiple other tumor types. Halda’s pipeline and platform may also enable the creation of novel targeted therapies beyond oncology.

"This acquisition further strengthens our deep oncology pipeline with an exciting lead asset in prostate cancer and a platform capable of treating multiple cancers and diseases beyond oncology, providing a potential mid- and long-term catalyst for growth," said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Innovative Medicine, Johnson & Johnson. "We look forward to combining Halda’s pipeline, platform and people with our world class R&D, commercial and manufacturing capabilities and advancing our goal of bringing these therapies to patients around the world."

"Many therapies lose effectiveness over time due to resistance. Halda’s innovative technology is designed to work even when cancers no longer respond to standard treatments using a novel mechanism that enables the selective killing of cancer cells," said John C. Reed, M.D., Ph.D., Executive Vice President, Innovative Medicine, R&D, Johnson & Johnson. "Results seen with HLD-0915 demonstrate impressive preliminary efficacy and a strong early safety profile in prostate cancer. We are eager to accelerate the ongoing Phase 1/2 clinical trial of HLD-0915 and progress a pipeline of novel product candidates based on RIPTAC technology​."

The planned acquisition underscores Johnson & Johnson’s longstanding commitment to prostate cancer and industry-leading oncology portfolio, adding new therapies with novel and complementary mechanisms of action. Halda’s pipeline of differentiated assets, if successful, will provide critical new options for patients.

About the Acquisition Agreement

Under the terms of the agreement, Johnson & Johnson will acquire Halda. The transaction will be accounted for as a business combination and is expected to close within the next few months, subject to antitrust clearance and other customary closing conditions. The Company expects dilution in 2026 of $0.15 to Adjusted Earnings Per Share (EPS) due to short-term financing and a non-recurring charge related to the equity awards for Halda employees upon closing. Johnson & Johnson will provide commentary on full year 2026 guidance during the fourth quarter earnings call on Wednesday, January 21, 2026.

(Press release, Johnson & Johnson, NOV 17, 2025, View Source [SID1234660042])

On November 17, 2025 Syntara Limited (ASX: SNT), a clinical-stage drug development company, reported that it has received a positive opinion on the submission of Orphan Drug Designation (ODD) from the European Medicines Agency (EMA) for its advanced clinical asset amsulostat (SNT-5505) for the treatment of myelofibrosis (MF).

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An ODD grant will provide numerous incentives for Syntara in the European Union (EU) as it develops amsulostat, including ten years market exclusivity upon approval, clinical trial protocol assistance, access to the centralised authorisation procedure in Europe, and certain fee reductions.

Amsulostat already has ODD in the US from the Food & Drug Administration (FDA) for the treatment of MF.

Myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material. Over time, this leads to progressive bone marrow failure. It can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years, with its cause remaining largely unknown.

Syntara recently announced positive top-line Phase 2a data for amsulostat in MF, with patients sub optimally controlled on ruxolitinib with 73% achieving at least a 50% reduction in total symptom score, and nearly half showing meaningful spleen volume reduction after a year of treatment. This sustained improvement in clinical measures of efficacy is backed up by excellent tolerability and no treatment-related adverse events.

Syntara has received feedback from the FDA on a recommended pathway for further development, and is progressing a design for the next trial of amsulostat.

Syntara CEO Gary Phillips commented: "Receipt of this positive opinion for Orphan Drug Desgination in the EU comes after detailed review of the amsulostat pre-clinical and clinical dossier by the EMA, providing further validation of the potential that the drug has to benefit myelofibrosis patients. We continue to engage with our advisors and regulatory authorities to design a clinical trial that leverages the product’s strong differentiating features as a well-tolerated and effective therapy. Our goal is to ensure the study design is compelling for investors and strategic partners by clearly demonstrating how amsulostat can positively impact the current standard of care."

(Press release, Syntara, NOV 17, 2025, https://mcusercontent.com/add2e2fa70ec3d0eeaf2a93cc/files/42cc5d05-d389-5ba0-606c-034c87587de6/03023812.pdf [SID1234660003])