On September 15, 2026 Summit Therapeutics Inc. (Nasdaq: SMMT) reported that updated overall survival (OS) results from the global Phase III HARMONi clinical trial featuring the novel, potential first-in-class investigational bispecific antibody ivonescimab were presented today at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC 2026) in Seoul, Republic of Korea.

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As Summit previously announced on July 22, 2026, ivonescimab plus platinum-doublet chemotherapy in the HARMONi trial continued to show a positive OS trend and a consistent efficacy and safety profile in Asian and western patients when compared to placebo plus chemotherapy.

"Updated results from the global Phase III HARMONi study show that ivonescimab combined with chemotherapy continued to demonstrate a consistent overall survival improvement compared with placebo plus chemotherapy in patients with EGFR-mutated non-small cell lung cancer following prior treatment with a third-generation EGFR TKI," said Antonio Passaro, M.D., Ph.D., Director of the Division of Thoracic Oncology, European Institute of Oncology (IEO) in Milan, Italy, and presenting author. "Importantly, with longer follow-up, the survival improvement observed in western patients was consistent with the global population, reinforcing the relevance of these results across geographic regions in a setting where patients continue to need additional treatment options after progression on EGFR-targeted therapy."

HARMONi Detailed Efficacy and Safety Results

The HARMONi study is evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who were previously treated with a third-generation EGFR tyrosine kinase inhibitor (TKI). The study demonstrated a statistically significant benefit in the primary analysis for progression-free survival (PFS), one of the study’s two primary endpoints, the other being OS.

In April 2025, the primary OS analysis was performed, whereby ivonescimab in combination with chemotherapy showed a positive trend without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI: 0.62 – 1.01; p=0.057). Median OS was 16.8 months for those patients administered ivonescimab plus chemotherapy vs. 14.0 months for those receiving placebo plus chemotherapy. At the time of the primary analysis, median follow-up time for western patients was 9.2 months which was less than the median OS.

An additional analysis was performed with a data cut-off date in June 2026, whereby most western patients have discontinued or completed two years of treatment (median follow-up time 23.2 months for western patients). Median follow-up time for Asian patients was 32.7 months (this was reached in April 2025 and Asian patient data was locked at the time of that analysis). The updated June 2026 analysis continued to show consistent, favorable OS results, with an OS hazard ratio of 0.76 (95% CI: 0.61 – 0.95; nominal p=0.0151) in the global intention-to-treat (ITT) population. An OS hazard ratio of 0.76 was demonstrated in the western patient subgroup (95% CI: 0.52 – 1.10), which was consistent with the ITT population and Asian subgroup.

Global ITT Overall Survival Analyses at Each Data Cut-Off

DCO: Apr 2025

(Primary Analysis)

DCO: Sept 2025*

DCO: June 2026*

Ivonescimab + Chemo

Placebo + Chemo

Ivonescimab + Chemo

Placebo + Chemo

Ivonescimab + Chemo

Placebo + Chemo

(n=219)

(n=219)

(n=219)

(n=219)

(n=219)

(n=219)

Median OS, ITT

16.8 mos

14.0 mos

16.8 mos

14.0 mos

16.8 mos

14.0 mos

Hazard Ratio, ITT

0.79

(95% CI: 0.62 – 1.01;
p=0.057)

0.78

(95% CI: 0.62 – 0.98; nominal p=0.0332)

0.76

(95% CI: 0.61 – 0.95; nominal p=0.0151)

DCO = data cut-off; ITT = intention-to-treat population; mos = months; chemo = chemotherapy

*DCO for Asian patients was Apr 2025 for both Sept 2025 and June 2026 analyses

With longer follow-up, western patients replicated the survival improvement seen in Asian patients, further reinforcing the regional consistency of the efficacy results observed in the global HARMONi study.

Western Subgroup of Overall Survival Analyses at Each Data Cut-Off

DCO: Apr 2025

DCO: Sept 2025

DCO: June 2026

Ivonescimab + Chemo

Placebo + Chemo

Ivonescimab + Chemo

Placebo + Chemo

Ivonescimab + Chemo

Placebo + Chemo

(n=83)

(n=82)

(n=83)

(n=82)

(n=83)

(n=82)

Median OS, Western Patients

Not Reached

14.0 mos

17.0 mos

14.0 mos

17.5 mos

14.0 mos

Hazard Ratio, Western Patients

0.98

(95% CI: 0.55 – 1.73)

0.84

(95% CI: 0.53 – 1.32)

0.76
(95% CI: 0.52 – 1.10)

Median follow-up, Western Patients

9.2 mos

13.7 mos

23.2 mos

DCO = data cut-off; ITT = intention-to-treat population; mos = months; chemo = chemotherapy

In this most recent analysis, ivonescimab continued to demonstrate an acceptable and manageable safety profile that was consistent with previous Phase III data of ivonescimab plus chemotherapy. No additional safety signals were noted in this latest HARMONi data cut.

"The updated HARMONi overall survival analysis presented at WCLC 2026 provides important additional evidence of the consistency of ivonescimab’s clinical profile across patient populations, with western patients showing consistent survival improvement to what was observed in Asian patients," stated Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit. "Together with the continued acceptable and manageable safety profile, these data reinforce our confidence in the HARMONi results as we work toward the potential approval of ivonescimab in the U.S."

"What continues to distinguish ivonescimab is not only the strength of these HARMONi results, but the expanding clinical data sets emerging across studies and tumor types, including recent positive results from HARMONi-2 and HARMONi-GI1 in biliary tract cancer," added Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit. "Together, these data reinforce our belief in the potential breadth of ivonescimab’s differentiated bispecific design as an important new therapeutic approach in oncology, beginning with EGFR-mutated non-small cell lung cancer and extending across our broader ambition to address serious needs in solid tumors where patients urgently need better options."

Summit’s Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) is based on the results from the HARMONi trial and has a Prescription Drug User Fee Act (PDUFA) goal action date of November 14, 2026.

HARMONi-2 Detailed OS Efficacy and Safety Results

Previously, key findings from the HARMONi-2 primary OS analysis were announced by Summit’s partner, Akeso Inc. Today, the full detailed results were presented at WCLC 2026, with highlights provided below. HARMONi-2 (AK112-303) is a single-region, multi-center Phase III study conducted in China and sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso.

In this protocol-specified interim analysis of OS, a secondary endpoint in the HARMONi-2 study, ivonescimab monotherapy demonstrated a statistically significant and clinically meaningful improvement compared to pembrolizumab monotherapy, achieving a hazard ratio (HR) of 0.73 (95% CI: 0.57, 0.95; p=0.009). A clinically meaningful benefit was demonstrated across important clinical subgroups, including those with PD-L1 low expression (PD-L1 Score 1-49%) and PD-L1 high expression (PD-L1 Score ≥ 50%), along with those with squamous and non-squamous histologies.

HARMONi-2 ITT (n=398)

Median Follow-up: 36.0 mos

Ivonescimab

(n=198)

Pembrolizumab

(n=200)

Median OS

30.8 mos

(95% CI: 25.4, 37.8)

22.6 mos

(95% CI: 17.8, 26.5)

OS Stratified HR

0.73

(95% CI: 0.57, 0.95; p=0.009)

24-Month KM OS Rate

57.9%

48.0%

36-Month KM OS Rate

45.0%

33.1%

ITT = intention-to-treat population; mos = months; CI = confidence interval, KM= Kaplan Meier method

HARMONi-2 Subgroup Analyses

Descriptive, not formally powered

Ivonescimab vs. Pembrolizumab

PD-L1 High (PD-L1 Score ≥50%)

HR = 0.58 (95% CI: 0.38, 0.89)

n=168

Median OS: NR vs. 23.2 mos

PD-L1 Low (PD-L1 Score 1-49%)

HR = 0.85 (95% CI: 0.61, 1.18)

n=230

Median OS: 28.5 mos vs. 22.1 mos

Squamous Histology

HR = 0.65 (95% CI: 0.45, 0.95)

n=181

Median OS: 30.5 mos vs. 19.3 mos

Non-Squamous Histology

HR = 0.79 (95% CI: 0.55, 1.14)

n=217

Median OS: 33.6 mos vs. 25.6 mos

Age <65

HR = 0.75 (95% CI: 0.51, 1.11)

n=182

Median OS: 32.8 mos vs. 25.0 mos

Age ≥65

HR = 0.72 (95% CI: 0.51, 1.01)

n=216

Median OS: 30.2 mos vs. 22.1 mos

Male

HR = 0.74 (95% CI: 0.56, 0.98)

n=333

Female

HR = 0.69 (95% CI: 0.38, 1.25)

n=65

NR = not reached; mos = months; CI=confidence interval; n = number

In this analysis, ivonescimab continued to demonstrate an acceptable and manageable safety profile in the HARMONi-2 study, which was consistent with previous Phase III studies of ivonescimab. No additional safety signals were noted in the HARMONi-2 study in this current data cut with longer treatment duration (median of 14 cycles of ivonescimab vs 10 cycles of pembrolizumab) compared to the previous data cut.

Treatment-Related Adverse Events

Median follow-up: 36.0 mos

Ivonescimab (n=198)

Pembrolizumab (n=200)

Serious TRAEs, n (%)

59 (29.9)

43 (21.6)

TRAEs Leading to Discontinuation, n (%)

8 (4.1)

10 (5.0)

TRAEs Leading to Death, n (%)

1 (0.5)

3 (1.5)

TRAEs = treatment-related adverse events; n = number; mos = months

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit’s license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This design is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Summit believes ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, iScience, 2025). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of ivonescimab’s design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, iScience, 2025) and increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs to these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently utilized in multiple Phase III clinical trials. Over 4,000 patients have been treated with ivonescimab in clinical studies globally and over 70,000 patients when considering those treated in a commercial setting in China, as noted by Akeso.

There are currently 16 Phase III clinical studies that are either announced, ongoing, or have been completed studying ivonescimab, five of which are Summit-sponsored global studies, one of which is a multiregional study sponsored by a cooperative group, and 10 of which are being or have been conducted in China by Akeso. Summit began its clinical development of ivonescimab in NSCLC, commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In 2025, Summit began enrolling patients in HARMONi-7. Summit expanded its Phase III clinical development program into colorectal cancer (CRC) in the fourth quarter of 2025 by initiating enrollment in HARMONi-GI3. In 2026, Summit announced initiation of HARMONi-GU1, a Phase II/III study in urothelial carcinoma (bladder cancer) with global clinical trial site activations planned to begin by the fourth quarter of 2026.

HARMONi is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR TKI (e.g., osimertinib). Detailed results of the study were provided in September 2025, and a Biologics License Application (BLA) was submitted to the United States Food and Drug Administration (FDA) for marketing authorization, which the FDA accepted for filing in January 2026; the goal Prescription Drug User Fee Act (PDUFA) date is November 14, 2026.

HARMONi-3 is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression. The clinical trial is evaluating the two histologies as individual, separately powered cohorts with independent statistical powering.

HARMONi-7 is a Phase III clinical trial evaluating ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

HARMONi-GI3 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC.

HARMONi-GU1 is a Phase II/III clinical trial evaluating ivonescimab plus the antibody drug conjugate (ADC) enfortumab vedotin (EV) compared to pembrolizumab plus EV as first-line therapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).

ILLUMINE is a Phase III study being conducted by GORTEC, a cooperative group dedicated to Head and Neck Oncology, in recurrent / metastatic head and neck squamous cell carcinoma (r/m HNSCC). ILLUMINE is a three-arm Phase III clinical trial designed to evaluate ivonescimab monotherapy, as well as ivonescimab in combination with ligufalimab, Akeso’s proprietary anti-CD47 monoclonal antibody, compared to monotherapy pembrolizumab in patients with PD-L1 positive r/m HNSCC.

Five Phase III ivonescimab clinical trials have read out to date, all five with positive data. Four of these five studies are in NSCLC, and one is in biliary tract cancer (BTC). In addition to Summit’s positive HARMONi study, Akeso has had positive read-outs in three single-region (China), randomized Phase III clinical trials, HARMONi-A, HARMONi-2, and HARMONi-6, for ivonescimab in NSCLC, including a statistically significant overall survival benefit in all three studies from China. Akeso has also reported a statistically significant OS benefit in the single-region (China), randomized Phase III HARMONi-GI1 trial in advanced BTC.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

HARMONi-GI1 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with durvalumab plus chemotherapy as a first-line treatment for patients with advanced BTC.

Akeso is actively conducting additional Phase III clinical studies in settings outside of NSCLC and biliary-tract cancer, including triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer, and pancreatic cancer.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024.

(Press release, Summit Therapeutics, SEP 15, 2026, View Source [SID1234670880])

On September 15, 2026 BostonGene, developer of the leading AI model for tumor and immune biology, reported an expansion of its scientific collaboration with Dana-Farber Cancer Institute to deepen the understanding of the complex biological mechanisms driving BRCA1- and BRCA2-associated breast cancers. The collaboration applies BostonGene’s foundation model of tumor and immune biology and multimodal AI to place individual tumors into a much broader biological context, enabling systematic discovery of the mechanisms that distinguish disease subtypes and potentially drive therapeutic response and resistance.

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Focusing on BRCA1/2-associated ER-positive breast cancer (BRCA ER+), TP53-mutant ER-positive breast cancer (TP53 ER+), and triple-negative breast cancer (TNBC), the initiative investigates why biologically similar-looking cancers behave differently, what drives response and resistance to targeted therapies, and how those insights can directly de-risk pipeline development by informing biomarker strategy and patient selection.

"Patients with hereditary BRCA1 and BRCA2 mutations face unique biological challenges, particularly across distinct disease presentations like ER+ breast cancer and TNBC," said Filipa Lynce, MD, Senior Physician at Dana-Farber Cancer Institute. "By combining detailed genomic and transcriptomic profiling with advanced analytics, this collaboration allows us to uncover critical molecular signatures underlying hereditary breast cancer to pave the way for more tailored, effective therapeutic strategies."

"Unraveling the crosstalk between DNA repair deficiencies and hormone signaling is fundamental to advancing precision oncology," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. "The opportunity is to move beyond describing these tumors by mutation or clinical subtype and understand the biology that actually differentiates them. By placing each patient into a much broader biological context, we can identify mechanisms that may explain disease behavior and ultimately translate those findings into better biomarker, patient-selection and therapeutic strategies."

By uncovering how DNA damage response pathways interact with hormone signaling, the collaboration demonstrates the capabilities of BostonGene’s AI-powered multimodal analytics in establishing high-resolution biological frameworks. The collaboration provides a model for how biologically grounded AI can turn relatively small, deeply characterized patient cohorts into insights that inform drug development, patient selection, and future clinical strategy.

(Press release, BostonGene, SEP 15, 2026, View Source [SID1234670879])

On September 15, 2026 Nuvation Bio Inc. (NYSE: NUVB), a global oncology company focused on tackling some of the toughest challenges in cancer treatment, reported new subgroup analyses from the pivotal TRUST-I and TRUST-II studies evaluating IBTROZI (taletrectinib) in both TKI- naïve and TKI-pretreated patients with advanced ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC). The data, presented at the IASLC 2026 World Conference on Lung Cancer (WCLC) in Seoul, Republic of Korea, demonstrated that IBTROZI delivered consistent efficacy regardless of prior chemotherapy exposure or ROS1 fusion partner, providing additional evidence supporting its use across a broad range of patients with advanced ROS1+ NSCLC.

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"The most important step for a patient with newly diagnosed non-small cell lung cancer is to conduct comprehensive biomarker testing to identify a targetable driver and start the right targeted therapy as early as possible," said Jorge Nieva, M.D., medical oncologist at USC Norris Comprehensive Cancer Center. "Guidelines recommend holding treatment until biomarker testing comes back, which can create pressure to begin chemotherapy first. These analyses offer reassurance that patients who do start chemotherapy before a ROS1 fusion is identified can still respond well once they transition to taletrectinib. We hope this gives clinicians added confidence to move promptly to targeted therapy as soon as biomarker testing confirms a ROS1 fusion."

"We’ve already been impressed by the durable efficacy of IBTROZI, with many responses lasting over four years, and now these new data answer critical questions about its consistency," said David Hung, M.D., Founder, President and Chief Executive Officer of Nuvation Bio. "These analyses show that patients derive a similar, powerful benefit from IBTROZI across multiple subgroups, which we hope gives clinicians even greater confidence in selecting IBTROZI for any patient with advanced ROS1+ NSCLC."

Previously at AACR (Free AACR Whitepaper) 2026, the pooled analysis of all TKI-naïve patients in the TRUST-I and TRUST-II studies presented showed a confirmed objective response rate (ORR) of 89.8% and a median duration of response (DOR) of 49.7 months. At WCLC, one of the new analyses presented in the poster revealed consistent response rates regardless of prior chemotherapy exposure.

Among TKI-naïve patients:

ORR was 90.0% in those with prior chemotherapy (n=30) and 89.8% in those with no prior chemotherapy (n=127).
Median DOR was 48.3 months and 54.3 months, respectively.
While this analysis shows that patients can respond to IBTROZI following prior chemotherapy, treatment guidelines continue to recommend waiting to begin treatment until biomarker results come back and initiating targeted therapy as soon as a ROS1 fusion is confirmed. These findings reinforce the importance of early biomarker testing and prompt transition to targeted therapy.

Additionally, both TKI-naïve and TKI-pretreated patients consistently benefited from IBTROZI regardless of ROS1 fusion partner. A fusion partner is the gene that merges with ROS1, resulting in a hybrid, cancer-driving protein that fuels tumor growth. The most common partner is CD74, which accounts for up to half of all ROS1 fusions in NSCLC.

Among TKI-naïve patients:

ORR was 89.5% in those with CD74 fusions (n=19) and 88.9% in those with non-CD74 fusions (n=18).
Median DOR was comparable between the two groups at 44.8 and 43.3 months, respectively, as was median progression-free survival (PFS) at 46.1 and 44.6 months.
With long-term follow-up, IBTROZI continued to demonstrate a manageable safety profile consistent with previous reports, with no new safety signals identified. The most common adverse events in the overall TRUST-I and TRUST-II pooled safety analyses were increased AST and ALT, diarrhea, nausea and vomiting, which were mostly low grade.

To review the poster, visit the Publications section of Nuvation Bio’s website.

About ROS1+ NSCLC
Each year, more than one million people globally are diagnosed with non-small cell lung cancer (NSCLC), the most common form of lung cancer. It is estimated that approximately 2% of patients with NSCLC have ROS1+ disease. About 35% of patients newly diagnosed with metastatic ROS1+ NSCLC have tumors that have spread to their brain. The brain is also the most common site of disease progression, with about 50% of previously treated patients developing central nervous system (CNS) metastases.

About IBTROZI
IBTROZI is an oral, potent, CNS-active, selective, next-generation ROS1-inhibitor therapy. On June 11, 2025, following Priority Review and Breakthrough Therapy designations for both TKI-naive and TKI-pretreated disease, the U.S. Food and Drug Administration (FDA) approved taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC. Learn more about taletrectinib in the U.S. at IBTROZI.com.

About the TRUST Clinical Program
The TRUST clinical program comprises three registrational studies evaluating the safety and efficacy of IBTROZI. TRUST-I (NCT04395677) and TRUST-II (NCT04919811) are Phase 2 single-arm studies evaluating IBTROZI for the treatment of adults with advanced ROS1+ NSCLC in China (N=173) and globally (N=189), respectively. The primary endpoint of both studies is confirmed objective response rate (cORR) as assessed by an independent review committee. TRUST-IV (NCT07154706) is a Phase 3 placebo-controlled study evaluating IBTROZI for the adjuvant treatment of adults with resected early-stage ROS1+ NSCLC. The study will enroll approximately 180 patients in the U.S., Canada, Europe, Japan and China. The primary endpoint is disease-free survival as determined by investigator, and the primary completion date is estimated to be in 2030. Nuvation Bio is also sponsoring TRUST-III (NCT06564324), a confirmatory randomized Phase 3 study evaluating IBTROZI versus crizotinib in 194 patients in China with advanced ROS1+ NSCLC who have not previously received ROS1 TKIs.

U.S. Indication
IBTROZI is indicated for the treatment of adult patients with locally advanced or metastatic ROS1+ non-small cell lung cancer (NSCLC).

IMPORTANT SAFETY INFORMATION FOR IBTROZI (taletrectinib)

WARNINGS AND PRECAUTIONS

Hepatotoxicity: Hepatotoxicity, including drug-induced liver injury and fatal adverse reactions, can occur. 88% of patients experienced increased AST, including 10% Grade 3/4. 85% of patients experienced increased ALT, including 13% Grade 3/4. Fatal liver events occurred in 0.6% of patients. Median time to first onset of AST or ALT elevation was 15 days (range: 3 days to 20.8 months).

Increased AST or ALT each led to dose interruption in 7% of patients and dose reduction in 5% and 9% of patients, respectively. Permanent discontinuation was caused by increased AST, ALT, or bilirubin each in 0.3% and by hepatotoxicity in 0.6% of patients.

Concurrent elevations in AST or ALT ≥3 times the ULN and total bilirubin ≥2 times the ULN, with normal alkaline phosphatase, occurred in 0.6% of patients.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, or fatal ILD or pneumonitis can occur. ILD/pneumonitis occurred in 2.3% of patients, including 1.1% Grade 3/4. One fatal ILD case occurred at the 400 mg daily dose. Median time to first onset of ILD/pneumonitis was 3.8 months (range: 12 days to 11.8 months).

ILD/pneumonitis led to dose interruption in 1.1% of patients, dose reduction in 0.6% of patients, and permanent discontinuation in 0.6% of patients.

QTc Interval Prolongation: QTc interval prolongation can occur, which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death. IBTROZI prolongs the QTc interval in a concentration-dependent manner.

In patients who received IBTROZI and underwent at least one post baseline ECG, QTcF increase of >60 msec compared to baseline and QTcF >500 msec occurred in 13% and 2.6% of patients, respectively. 3.4% of patients experienced Grade ≥3. Median time from first dose of IBTROZI to onset of ECG QT prolongation was 22 days (range: 1 day to 38.7 months). Dose interruption and dose reduction each occurred in 2.8% of patients.

Significant QTc interval prolongation may occur when IBTROZI is taken with food, strong and moderate CYP3A inhibitors, and/or drugs with a known potential to prolong QTc. Administer IBTROZI on an empty stomach. Avoid concomitant use with strong and moderate CYP3A inhibitors and/or drugs with a known potential to prolong QTc.

Hyperuricemia: Hyperuricemia can occur and was reported in 14% of patients, with 16% of these requiring urate-lowering medication without pre-existing gout or hyperuricemia. 0.3% of patients experienced Grade ≥3. Median time to first onset was 2.1 months (range: 7 days to 35.8 months). Dose interruption occurred in 0.3% of patients.

Myalgia with Creatine Phosphokinase (CPK) Elevation: Myalgia with or without CPK elevation can occur. Myalgia occurred in 10% of patients. Median time to first onset was 11 days (range: 2 days to 10 months).

Concurrent myalgia with increased CPK within a 7-day time period occurred in 0.9% of patients. Dose interruption occurred in 0.3% of patients with myalgia and concurrent CPK elevation.

Skeletal Fractures: IBTROZI can increase the risk of fractures. ROS1 inhibitors as a class have been associated with skeletal fractures. 3.4% of patients experienced fractures, including 1.4% Grade 3. Some fractures occurred in the setting of a fall or other predisposing factors. Median time to first onset of fracture was 10.7 months (range: 26 days to 29.1 months). Dose interruption occurred in 0.3% of patients.

Embryo-Fetal Toxicity: Based on literature, animal studies, and its mechanism of action, IBTROZI can cause fetal harm when administered to a pregnant woman.

ADVERSE REACTIONS

Among patients who received IBTROZI, the most frequently reported adverse reactions (≥20%) were diarrhea (64%), nausea (47%), vomiting (43%), dizziness (22%), rash (22%), constipation (21%), and fatigue (20%).

The most frequently reported Grade 3/4 laboratory abnormalities (≥5%) were increased ALT (13%), increased AST (10%), decreased neutrophils (5%), and increased creatine phosphokinase (5%).

DRUG INTERACTIONS

Strong and Moderate CYP3A Inhibitors/CYP3A Inducers and Drugs that Prolong the QTc Interval: Avoid concomitant use.
Gastric Acid Reducing Agents: Avoid concomitant use with PPIs and H2 receptor antagonists. If an acid-reducing agent cannot be avoided, administer locally acting antacids at least 2 hours before or 2 hours after taking IBTROZI.
OTHER CONSIDERATIONS

Pregnancy: Please see important information in Warnings and Precautions under Embryo-Fetal Toxicity.
Lactation: Advise women not to breastfeed during treatment and for 3 weeks after the last dose.
Effect on Fertility: Based on findings in animals, IBTROZI may impair fertility in males and females. The effects on animal fertility were reversible.
Pediatric Use: The safety and effectiveness of IBTROZI in pediatric patients has not been established.
Photosensitivity: IBTROZI can cause photosensitivity. Advise patients to minimize sun exposure and to use sun protection, including broad-spectrum sunscreen, during treatment and for at least 5 days after discontinuation.

(Press release, Nuvation Bio, SEP 15, 2026, View Source [SID1234670878])

On September 15, 2026 Jubilant Therapeutics Inc., a clinical-stage biopharmaceutical company advancing precision therapies for hematological malignancies, reported the presentation of the first clinical data from its ongoing Phase 1/2 study of JBI-802, the company’s first-in-class oral dual LSD1/HDAC6 inhibitor, at the Society of Hematologic Oncology (SOHO) 2026 Annual Meeting, which took place during September 9-12, 2026, in Houston, Texas. The data demonstrated the first clinical evidence supporting dual inhibition of LSD1 and HDAC6 as a differentiated therapeutic approach for patients with myeloproliferative neoplasms (MPNs), a group of blood cancers, including essential thrombocythemia (ET) and polycythemia vera (PV).

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The presentation titled, ‘Breaking the Limits of LSD1 Inhibition: Dual LSD1/HDAC6 Epigenetic Targeting with JBI-802 in MPNs,’ was given by Dr. Sandra Aung, Chief Development Officer, and reported clinical activity across patients (n = 12) with ET, PV, myelofibrosis (MF) and myelodysplastic syndrome/ myeloproliferative neoplasm (MDS/MPN), with rapid, sustained and durable, dose-dependent reductions in platelet counts with a manageable safety profile.

Clinical Highlights

Rapid and Meaningful Platelet Reductions Across MPN Subtypes

As of June 30, 2026, twelve patients across four dose cohorts (5 mg, 7 mg, 15 mg, and 20 mg) were evaluated in the dose-escalation portion of the study.

Key findings included:

Platelet reductions were observed across ET, PV, MF and MDS/MPN patients, with clinical activity seen across JAK2, CALR, and MPL-mutated disease.
At the 15 mg dose level, all three patients achieved rapid and substantial platelet reductions of 75%, 72%, and 81%, respectively within the first 30 days of treatment.
9 of 9 ET/PV patients, evaluable for platelet reduction, achieved reductions ranging from 36-91%. Four ET/PV patients with extreme thrombocytosis (baseline platelet counts >1,000 × 10⁹/L) achieved rapid platelet reductions of 30% to 75% within the first 30 days of treatment and subsequently achieved maximum platelet reductions ranging from 72% to 91% during treatment.
Platelet responses were durable and maintained through dose modification, supporting a controllable pharmacokinetic-pharmacodynamic relationship.
Manageable Safety Profile

As of June 30, 2026, data cutoff:

No investigator assessed dose-limiting toxicities were observed at the 5 mg, 7 mg, or 15 mg dose levels.
One dose-limiting thrombocytopenia event was observed at the 20 mg dose level and was successfully managed through protocol-defined dose modification. Following dose reduction to 10 mg, the patient remains on treatment with platelet counts maintained within the normal range.
Of the 12 treatment-emergent adverse events (TEAEs) reported, 10 were Grade 1 or 2 in severity and two were Grade 3 or higher. No patients discontinued treatment due to thrombocytopenia or treatment-related adverse events.
"These preliminary findings highlight several characteristics that we believe are important for the long-term management of myeloproliferative neoplasms," said Daniel O’Connor, President and Chief Executive Officer of Jubilant Therapeutics. "In addition to rapid and sustained reductions in platelet counts across multiple MPN subtypes, JBI-802 has demonstrated a favorable tolerability profile, with patients remaining on treatment for more than six months and continuing to derive clinical benefit. We are particularly encouraged by the combination of meaningful clinical activity, prolonged treatment exposure, and a pharmacokinetic profile that supports flexible dose adjustment. Together, these data suggest JBI-802 has the potential to offer a differentiated therapeutic option for patients living with these chronic hematologic malignancies."

A Novel Approach to Epigenetic Targeting in MPNs

JBI-802 is the only oral dual LSD1/HDAC6 inhibitor currently in clinical development and is administered once daily. JBI-802 was designed to simultaneously inhibit LSD1 and HDAC6, two complementary epigenetic regulators involved in the abnormal blood cell proliferation and production characteristic of MPNs. Preclinical studies have suggested that dual inhibition may provide broader biological activity than selective inhibition of either pathway alone.

The molecule has a short half-life of approximately 1.5 to 2 hours and is rapidly cleared from circulation, a profile that may offer several advantages for chronic treatment including predictable systemic exposure, rapid reversibility of pharmacologic effects, flexible dose titration and the ability to promptly manage on-target hematologic effects through dose titration.

The ongoing Phase 1/2 study (NCT07612280) is evaluating JBI-802 in patients with relapsed, refractory, or treatment-intolerant MPNs. Study objectives include evaluation of safety and tolerability, identification of the recommended Phase 2 dose, and assessment of preliminary efficacy through platelet reduction, durability of hematologic response, and molecular outcomes.

Enrollment is ongoing and Jubilant Therapeutics expects to present additional efficacy, safety, and molecular response data as the program advances.

The poster is available on the Jubilant website at SOHO 2026 – JBI-802 Poster

About Myeloproliferative Neoplasms (MPNs)

Myeloproliferative neoplasms (MPNs) are a group of chronic blood cancers driven by mutations in genes such as JAK2, CALR, and MPL, causing the bone marrow to overproduce blood cells. Essential thrombocythemia (ET) is characterized by excess platelet production, while polycythemia vera (PV) is characterized by excess red blood cell production; both are associated with an increased risk of blood clots and can progress to more advanced disease over time. Despite available treatments, many patients with ET and PV continue to experience inadequate disease control, underscoring the need for new therapeutic approaches.

About JBI-802

JBI-802 is an orally administered dual inhibitor of lysine-specific demethylase 1, or LSD1, and histone deacetylase 6, or HDAC6. JBI-802 is the only dual LSD1/HDAC6 inhibitor currently in clinical development. JBI-802 simultaneously targets multiple disease-relevant processes, including abnormal megakaryocyte differentiation, platelet production, leukocyte proliferation and inflammatory signaling. JBI-802 is being evaluated in an ongoing Phase 1/2 clinical study in patients with essential thrombocythemia, or ET, and other thrombocytosis-predominant myeloid malignancies. Emerging clinical data has demonstrated rapid reductions in platelet counts and activity across multiple molecular subtypes of disease.

(Press release, Jubilant Therapeutics, SEP 15, 2026, View Source [SID1234670877])

On September 15, 2026 Tempest Therapeutics, Inc. (Nasdaq: TPST) ("Tempest"), a clinical-stage biotechnology company developing in vivo CAR-T therapies designed to reset dysfunctional immunity in cancer and autoimmune disease, reported that it has entered into an exclusive option agreement with Hebei Senlang Biotechnology Co., Ltd. ("Senlang").

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The agreement provides Tempest with an exclusive option to license Senlang’s CD7-targeted lentiviral vector platform and a portfolio of in vivo CAR-T product candidates. The portfolio includes a BCMA/GPRC5D dual-targeting in vivo CAR-T candidate currently in Phase 1 dose escalation for relapsed/refractory multiple myeloma, as well as additional candidates for hematologic malignancies and autoimmune diseases.

"This agreement represents an important step in building Tempest as a multi-platform in vivo CAR-T company focused on immune reset for oncology and autoimmune indications," said Matt Angel, Ph.D., President and Chief Executive Officer of Tempest. "Upon exercise of the option, the CD7-targeted lentiviral platform would complement our targeted LNP platform, providing two distinct approaches to generating CAR-T cells directly within patients. The lead program is currently in clinical development and has demonstrated in vivo CAR-T generation and expansion, providing encouraging early clinical support."

Senlang’s proprietary platform uses targeted lentiviral vectors to deliver CAR transgenes to endogenous CD7-positive T cells and natural killer cells, generating CAR-T and CAR-NK cells directly within the patient. The approach is designed to avoid the individualized cell collection and external manufacturing required for conventional autologous CAR-T therapy. The lead program encodes a dual-targeting CAR directed against BCMA and GPRC5D, two clinically validated targets in multiple myeloma. Targeting both antigens may broaden malignant plasma-cell coverage and reduce the potential for tumor escape associated with the loss or downregulation of a single antigen.

The candidate is currently being evaluated in an ongoing Phase 1 dose-escalation study in patients with relapsed/refractory multiple myeloma. Early clinical observations at the current highest evaluable dose demonstrate successful generation and expansion of CAR-T cells in vivo. As of August 25, 2026, no Grade 3 or higher cytokine release syndrome and no immune effector cell-associated neurotoxicity syndrome were observed. The initial safety profile supports continued dose escalation, and patient enrollment and follow-up remain ongoing.

"Together, our targeted LNP and targeted lentiviral vector platforms are intended to support a broad portfolio of immune reset therapies," said Dr. Angel. "The LNP platform offers a potentially repeatable approach to transient CAR expression, while the lentiviral platform is designed to support durable CAR-cell generation. These complementary capabilities provide Tempest with the flexibility to match the delivery approach to the biology and treatment requirements of different cancers and autoimmune diseases."

Tempest and Senlang will continue to evaluate the Phase 1 results and the broader product portfolio during the option period. Tempest expects to provide additional information regarding the program as the clinical data mature.

About Senlang’s CD-7-Directed Lentiviral Platform

Senlang has a pipeline of in vivo CAR-T cell programs utilizing its CD7-directed lentiviral platform, which is designed to selectively deliver CAR payloads to endogenous CD7-positive T cells and NK cells, enabling in vivo generation of antigen-directed CAR immune cells. Proprietary nanobody-based retargeting promotes selective cell engagement and efficient transduction, while an engineered detargeted cocal envelope is intended to improve serum resistance, particle stability, and functional delivery in the bloodstream. Producer-cell engineering adds an immune-shielding feature to the lentiviral delivery particles, helping them remain functional longer in the bloodstream and improving delivery to CD7-positive immune cells. In preclinical studies, the platform demonstrated enhanced transduction in whole blood and resting PBMCs, and a single low-dose administration produced efficient in vivo transduction, rapid CAR-cell expansion, tumor-site enrichment, and durable tumor regression in mouse models.

(Press release, Tempest Therapeutics, SEP 15, 2026, View Source [SID1234670873])