On March 26, 2025 Keymed Biosciences Inc. (HKEX: 02162) reported its annual results of 2024, along with a corporate update (Press release, Keymed Biosciences, MAR 26, 2025, View Source [SID1234651479]).

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Rapid development of our pipeline products

Stapokibart (CM310) (IL-4Rα antibody)

Three new drug applications of Stapokibart for the treatment of moderate-to-severe atopic dermatitis (AD) in adults, chronic rhinosinusitis with nasal polyposis (CRSwNP) and seasonal allergic rhinitis have been approved by the NMPA. By the end of 2024, Stapokibart resisted strong sales and recorded revenue of approximately RMB40 million within three and a half months.

In September 2024, the new drug application of Stapokibart injection for the treatment of moderate-to-severe atopic dermatitis in adults was approved by the NMPA. The phase III clinical study results indicated that at week 52, the rates of achieving EASI-75 for the Stapokibart group and the placebo-to-Stapokibart group were 92.5% and 88.7%, respectively. The EASI-90 response rates were 77.1% and 65.6%, respectively. The rates of achieving an IGA score of 0 or 1 point with a reduction of ≥ 2 points from baseline were 67.3% and 64.2%, respectively. Additionally, the rates of achieving a weekly average reduction of ≥ 4 points from baseline in the daily PP-NRS score were 67.3% and 60.5%, respectively. Long-term treatment with Stapokibart can consistently improve dermatitis symptoms and quality of life in subjects with moderate-to-severe AD. During the maintenance period, only one subject (0.9%) experienced a relapse.
In December 2024, the new drug application of Stapokibart injection for the treatment of chronic rhinosinusitis with nasal polyps was approved by the NMPA. The study results showed that the data from the Phase III clinical trial was positive. Compared to the placebo, Stapokibart significantly reduced nasal polyps (NPS improvement of 2.3 from baseline) and alleviated nasal congestion (NCS improvement of 0.7 from baseline) after 24 weeks. The differences were highly statistically significant (P < 0.0001). Additionally, it effectively relieved rhinosinusitis, restored sense of smell, improved nasal symptoms, and enhanced quality of life.
In February 2025, the new drug application of Stapokibart injection for the treatment of seasonal allergic rhinitis was approved by the NMPA. We advanced and completed the data unblinding and statistical analysis for the Phase III clinical study of Stapokibart injection for the treatment of seasonal allergic rhinitis (SAR). The study findings demonstrate that during the pollen season, in comparison with the standard treatment group, which consists of nasal spray hormones combined with antihistamine drugs, the administration of Stapokibart for two weeks effectively controls the typical nasal allergic symptoms of patients, including runny nose, nasal congestion, nasal itching, and sneezing. The least-squares mean (LSMean) of the inter-group difference is -1.3, and its 95% confidence interval (CI) is also -1.3, indicating a highly significant statistical difference (P = 0.0008). This difference far exceeds the minimal clinically important difference (MCID) of 0.23, clearly demonstrating substantial clinical benefits. Moreover, Stapokibart can effectively alleviate ocular allergic symptoms such as eye itching or burning, eye tearing or watering, and eye redness. It comprehensively enhances the quality of life of patients and exhibits excellent safety.
In February 2024, we launched a randomized, double-blinded, placebo-controlled Phase III clinical study to evaluate the efficacy and safety of Stapokibart injection in adolescent subjects with moderate-to-severe AD.
In May 2024, we initiated a randomized, double-blinded, placebo-controlled Phase III clinical study to evaluate the efficacy and safety of Stapokibart injection in subjects with nodular prurigo. As of the date of this announcement, the patient enrollment for this clinical study is in progress.
In June 2024, the long-term efficacy and safety data from the Phase III clinical trial of Stapokibart injection for the treatment of moderate-to-severe AD were presented by way of oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024.
In October 2024, the full text of the 52-week efficacy and safety data of the Phase III clinical study was published in the《Allergy》, the top international journal in allergy and immunology field.
CMG901/AZD0901 (Claudin 18.2 ADC)
AstraZeneca has conducted multiple clinical studies regarding CMG901 (AZD0901) for the indications of gastric cancer, pancreatic cancer and biliary tract cancer, including the Phase III clinical trial for 2L+ gastric cancer, Phase II clinical trial for 1L gastric cancer, Phase II clinical trial for 1L pancreatic cancer, and Phase II clinical trial for 2L+ biliary tract cancer.
In June 2024, the data from the Phase I clinical study of CMG901 (AZD0901) in the treatment of advanced G/GEJ cancer were presented by way of oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024. On 6 January 2025, the data from the Phase I clinical study was released on the international authoritative oncology journal, The Lancet Oncology. The clinical data indicated that the median progression free survival (mPFS) for all 93 patients with Claudin 18.2-high expressing G/GEJ cancer was 4.8 months, and the median overall survival (mOS) was 11.8 months.
CM313 (CD38 antibody)

In 2024, we initiated and advanced a multi-center, open-label Phase I/II clinical study.
In June 2024, a research paper titled "A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia" was published in The New England Journal of Medicine. 95.5% of patients achieved a platelet count of ≥50 × 109/L within 8 weeks upon the first acceptance of CM313 infusion, and the durable platelet count response rate (defined as a platelet count of ≥50 × 109/L observed six or more times among the final eight platelet counts) was 63.6%.
In July 2024, we completed Phase Ib/IIa clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of CM313 injection in subjects with SLE. We plan to initiate a Phase II clinical study in the first half of 2025.
In 2024, we initiated a randomized, double-blinded, placebo-controlled Phase II clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of CM313(SC) injection in subjects with primary immune thrombocytopenia. The first patient was enrolled and dosed in November 2024.
We initiated a randomized, double-blinded, placebo-controlled Phase II clinical study to evaluate the safety and efficacy of CM313(SC) injection in subjects with IgA nephropathy in early 2025. As of the date of this announcement, preparations for patient enrollment are underway for this study.
CM512 (TSLP x IL-13 bispecific antibody)

We have initiated a randomized, double-blinded, single/multiple dose-escalation, placebo-controlled Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacokinetics and immunogenicity of CM512 in healthy subjects and patients with moderate-to-severe atopic dermatitis, with enrollment of the first subject completed in September 2024. The overseas Phase I clinical trial evaluating CM512 for the treatment of asthma was initiated in the first quarter of 2025.
CM336 (BCMAxCD3 bispecific antibody)

Continuously proceeded with a multi-center, open-label Phase I/II clinical study to assess CM336 injection in treating patients with relapsed or refractory multiple myeloma. As of the date of this announcement, the product is currently in the dose-expansion phase of Phase I/II clinical study.
In December 2024, the latest data of the phase I/II clinical study of CM336 for relapsed or refractory multiple myeloma was presented as a poster at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.
CM383 (Aβ protofibrils antibody)

As of the date of this announcement, the enrollment of all subjects in the Phase Ia clinical study of CM383 in healthy subjects was completed;
In November 2024, the enrollment of the first subject in Phase Ib clinical study of CM383 in patients with mild cognitive dysfunction of Alzheimer’s disease origin and mild Alzheimer’s disease was completed.
CM518D1 (CDH17 ADC)

We submitted IND application to CDE, and planned to conduct a multi-center, open-label Phase I/II clinical trial for evaluation of CM518D1 in treatment of patients with advanced solid tumors.
CM355/ICP-B02 (CD20 x CD3 bispecific antibody)

We are conducting a Phase I/II clinical trial in China to assess the safety, tolerability, PK, and the preliminary anti-tumor activity of CM355 in r/r NHL. Dose escalation of the intravenous infusion formulation ("IV") was completed and the subcutaneous formulation ("SC") is being evaluated. Our preliminary data of both IV and SC formulations have shown good efficacy of CM355 in patients with follicular lymphoma ("FL") and DLBCL.
CM350 (GPC3 x CD3 bispecific antibody)

Continuously proceeded with a Phase I/II clinical study in 2024 to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of CM350 in patients with advanced solid tumors. As of the date of this announcement, the product is currently in the dose-escalation of Phase I/II clinical study.
CM369/ICP-B05 (CCR8 antibody)

We are conducting a Phase I trial to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of CM369 in subjects with advanced solid tumors and relapsed/refractory NHL. Dose escalation of CM369 has been escalated up to 450 mg in solid tumor and 600 mg in NHL, CM369 was well tolerated with no DLTs nor ≥grade3 TRAEs observed. The preliminary results demonstrated a favorable PK profile with sufficient exposure for target coverage and regulatory T-cell depletion.
CM380 (GPRC5D×CD3 bispecific antibody)

Preclinical studies indicated that CM380 had favorable antitumor effects and was well tolerated. As of the date of this announcement, we are planning to conduct a multi-center, open-label Phase I/II clinical study for evaluation of CM380 in treatment of patients with relapsed or refractory multiple myeloma.
Financial and Business Highlights

Actively explore diversified BD models to maximize the global value of the pipeline.

In July 2024, Chengdu Keymed entered into a license agreement with Belenos Biosciences,Inc. The license agreement grants Belenos the exclusive rights to develop, manufacture,and commercialize the Group’s drug candidates CM512 and CM536 globally (excluding the Greater China region). In return, Chengdu Keymed shall receive an upfront and nearterm payment of US$15 million, and iBridge HK shall receive approximately 30.01% of the equity interest in Belenos as consideration. Subject to achievement of certain development, regulatory and commercial milestones, Chengdu Keymed may also receive additional payments up to US$170 million. As of the date of this announcement, Belenos is planning to initiate a Phase I clinical trial evaluating CM512 for the treatment of asthma.
In November 2024, Chengdu Keymed and Platina Medicines Ltd ("PML") entered into an exclusive license agreement. The license agreement grants PML the exclusive right to develop, manufacture and commercialize CM336 globally excluding Mainland China, Hong Kong, Macau and Taiwan. In return, the Group shall receive an upfront and near-term payment of US$16 million and a minority equity interest in Ouro Medicines, LLC ("Ouro Medicines") as part of the consideration. Ouro Medicines is the parent company of PML and owns 100% of the equity interest in PML. The Group may also receive additional payments of up to US$610 million subject to achievement of certain clinical, regulatory and commercial milestones and is also entitled to receive tiered royalties on net sales of CM336 and related products from PML.
In January 2025, Chengdu Keymed entered into an exclusive out-license agreement with Timberlyne Therapeutics, Inc. The license agreement grants the target company the exclusive right to develop, manufacture and commercialize CM313 globally (excluding Mainland China, Hong Kong, Macau and Taiwan). In return, the Group shall receive an upfront and near-term payment of US$30 million and equity interest of the target company, being the largest shareholder of this company. The Group may also receive additional payments up to US$337.5 million subject to achievement of certain sales and development milestones. The Group is also entitled to receive tiered royalties on net sales from the target company.
In January 2025, Chengdu Keymed, Beijing InnoCare and the Joint Venture have entered into the Agreement with Prolium for the development and commercialization of CM355. Under the terms of the Agreement, Prolium will have the exclusive right to develop, register, manufacture, and commercialize CM355 globally in non-oncology indications and in oncology indications outside of Asia.
Rapid expansion of workforce and production facilities

As of December 31, 2024, we had 1,300 full-time employees in total, including over 240 employees engaging in commercialization and nearly 400 employees engaging in drug discovery and clinical operations. We will continue to recruit talents to meet the growing needs of commercialization, research and development, clinical, production and operation of the Company.
As of the date of this announcement, the production capacity of our production base has reached 20,000 litres in total, and all the designs thereof are in compliance with the requirements of cGMP of the NMPA and FDA.
Financial highlights

As of December 31, 2024, the Company generated a total annual revenue of RMB 430 million, representing a 21% year-on-year increase. This includes about RMB 40 million in sales revenue from Stapokibart over three and a half months and RMB 390 million in licensing revenue from BD agreements. Throughout 2024, the company continued advancing its differentiated pipeline development and clinical research, with R&D expenditures reaching approximately RMB 730 million, a 23% year-on-year increase. The company maintained a strong cash position with total cash on hand of approximately RMB 2.1 billion.

Moving forward, Keymed will continue to establish, and refine its technology platforms, rapidly advancing the development of pipeline candidates in China and globally. The company will comprehensively drive the commercialization of approved product and indications. Concurrently, Keymed will proactively explore strategic partnerships worldwide to accelerate global patient access to its drug candidates through diversified BD models. The company plans to further recruit talent in commercial sales, clinical development, and manufacturing, expand cGMP-compliant production capacity, reduce costs, enhance operational efficiency, and remain committed to developing, producing, and commercializing innovative therapies that are globally competitive, high-quality, and affordable for patients worldwide.

On March 26, 2025 Johnson & Johnson (NYSE:JNJ) reported results for the gold standard endpoint in cancer treatment of overall survival (OS) from the Phase 3 MARIPOSA study (Press release, Johnson & Johnson, MAR 26, 2025, View Source [SID1234651478]). Head-to-head comparison data versus osimertinib showed RYBREVANT (amivantamab-vmjw) plus LAZCLUZE (lazertinib) significantly extended OS in the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. Median OS is projected to exceed one year beyond the median of three years observed with osimertinib and has not yet been reached. This is the first and only study to show a statistically significant and clinically meaningful OS improvement over osimertinib. New compelling data were presented during a proffered paper session at the 2025 European Lung Cancer Congress (ELCC) (Abstract #4O).1

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"The survival curve tells a clear story. RYBREVANT plus LAZCLUZE helps patients live longer, and the benefit keeps growing over time," said trial investigator Professor Nicolas Girard*, M.D., Ph.D., Head of Medical Oncology, Institut Curie, and Professor of Thoracic Oncology and Respiratory Medicine at the Paris-Saclay University, France. "We see the gap between the survival curves continue to widen, which is exactly what we want to see in lung cancer treatment to improve outcomes for patients. These results reinforce that we are entering a new era for EGFR-mutated non-small cell lung cancer; with this evidence in hand, we need to ensure every patient gets the most effective treatment in the first line for the best possible chance at longer survival."

Unlike progression-free survival (PFS), which tracks the time a treatment keeps a patient’s cancer from progressing, OS helps patients understand the impact therapy could have on the ability to live longer from the start of treatment. Extending life expectancy is the most meaningful indicator of a treatment’s impact.

At a median follow-up of 37.8 months, patients treated with the chemotherapy-free regimen of first-line RYBREVANT plus LAZCLUZE had a significantly longer OS compared to those receiving osimertinib (hazard ratio [HR], 0.75; 95 percent confidence interval [CI], 0.61-0.92; nominal P<0.005). Median OS for RYBREVANT plus LAZCLUZE has not yet been reached, indicating that survival benefits continue to extend beyond the measured follow-up period (not reached [NR]; 95 percent CI, 42.9-NR). Comparatively, median OS for osimertinib-treated patients was 36.7 months (95 percent CI, 33.4-41.0) and consistent with prior studies with osimertinib. Fifty-six percent of patients treated with RYBREVANT and LAZCLUZE were alive at three and a half years compared to 44 percent of patients on osimertinib. Projections based on survival data suggest RYBREVANT plus LAZCLUZE could extend median OS by at least 12 months compared to osimertinib.1

The RYBREVANT combination also prolonged multiple secondary endpoints vs osimertinib, including intracranial PFS, intracranial duration of response (DOR) and intracranial overall response rate (ORR). Notably, RYBREVANT plus LAZCLUZE prolonged time to symptomatic progression (TTSP) – the time from treatment randomization to the onset of lung cancer symptoms – by more than 14 months compared to osimertinib (43.6 months vs 29.3 months; HR, 0.69; 95 percent CI, 0.57–0.83; nominal P<0.001). This is a key patient-centered measure, highlighting how long quality of life can be preserved before lung cancer symptoms emerge.1

"Right now, only twenty percent of patients with EGFR-positive NSCLC survive beyond five years. These MARIPOSA results suggest that RYBREVANT plus LAZCLUZE can change this dire statistic that has been stagnant for far too long," said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. "This regimen isn’t just extending survival, it’s offering hope. By using RYBREVANT plus LAZCLUZE first, we’re delaying the need for chemotherapy and giving patients and their families more time."

The safety profile of RYBREVANT plus LAZCLUZE was consistent with the primary analysis, with adverse event (AE) rates comparable to other RYBREVANT regimens. No new safety signals were identified with the additional longer-term follow-up. Most AEs occurred early during RYBREVANT and LAZCLUZE treatment.1 RYBREVANT research findings suggest that implementing prophylactic measures during the first four months of RYBREVANT and LAZCLUZE treatment may significantly reduce the risk of skin reactions, infusion-related reactions and venous thromboembolic events.2,3,4

The MARIPOSA study met its primary endpoint in October 2023, showing a statistically significant and clinically meaningful improvement in PFS compared to osimertinib.

RYBREVANT plus LAZCLUZE is approved in the United States, Europe and other markets around the world for patients with first-line EGFR-mutated NSCLC. These OS results will be shared with health authorities globally.

About the MARIPOSA Study

MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT in combination with LAZCLUZE versus osimertinib and versus LAZCLUZE alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines**) as assessed by BICR. Secondary endpoints include OS, ORR, DOR, PFS2 and intracranial PFS.5

About RYBREVANT

RYBREVANT (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe and other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.6

RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.

RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with LAZCLUZE (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin-pemetrexed) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR TKI.

In February 2025, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of SC amivantamab and LAZCLUZE in Europe for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:

Amivantamab-vmjw (RYBREVANT) plus lazertinib (LAZCLUZE) as a Category 1 recommendation for first-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.7†‡
Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a Category 1 recommendation for patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.7†‡
Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a Category 1 recommendation for first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC.7†‡
Amivantamab-vmjw (RYBREVANT) as a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.7†‡
In addition to the Phase 3 MARIPOSA Study, RYBREVANT is being studied in multiple clinical trials in NSCLC, including:

The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT (with or without LAZCLUZE) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations after disease progression on or after osimertinib.8
The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.9
The Phase 3 PALOMA-3 (NCT05388669) study assessing LAZCLUZE with subcutaneous (SC) amivantamab compared to RYBREVANT in patients with EGFR-mutated advanced or metastatic NSCLC.10
The Phase 2 PALOMA-2 (NCT05498428) study assessing SC amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.11
The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of SC amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for SC amivantamab delivery.12
The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT in patients with advanced NSCLC.13
The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT in combination with LAZCLUZE and LAZCLUZE as a monotherapy in patients with advanced NSCLC with EGFR mutations.14
The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT and capmatinib combination therapy in locally advanced or metastatic NSCLC.15
The Phase 1/2 swalloWTail (NCT06532032) study assessing RYBREVANT and docetaxel combination therapy in patients with metastatic NSCLC.16
The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT and cetrelimab combination therapy in locally advanced or metastatic NSCLC.17
The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT in combination with LAZCLUZE in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.18
The Phase 2 COPERNICUS (NCT06667076) study combining developments in treatment administration and prophylactic supportive care in representative US patients with common EGFR-mutated NSCLC treated with SC amivantamab in combination with LAZCLUZE or chemotherapy.19
The Phase 2 COCOON (NCT06120140) study assessing the effectiveness of a proactive dermatologic management regimen given with first-line RYBREVANT and LAZCLUZE in patients with EGFR-mutated advanced NSCLC.20
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About LAZCLUZE

In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE (marketed as LECLAZA in South Korea). LAZCLUZE is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. An analysis of the efficacy and safety of LAZCLUZE from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.21

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.22,23 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.24 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.25 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.22,23,26,27,28,29 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.30 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.31,32 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.33 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.34

IMPORTANT SAFETY INFORMATION6,35

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

RYBREVANT can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.

RYBREVANT with LAZCLUZE

RYBREVANT in combination with LAZCLUZE can cause infusion-related reactions. In MARIPOSA (n=421), IRRs occurred in 63% of patients treated with RYBREVANT in combination with LAZCLUZE, including Grade 3 in 5% and Grade 4 in 1% of patients. The incidence of infusion modifications due to IRR was 54% of patients, and IRRs leading to dose reduction of RYBREVANT occurred in 0.7% of patients. Infusion-related reactions leading to permanent discontinuation of RYBREVANT occurred in 4.5% of patients receiving RYBREVANT in combination with LAZCLUZE.

RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population (n=281), IRR occurred in 50% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (3.2%) adverse reactions. The incidence of infusion modifications due to IRR was 46%, and 2.8% of patients permanently discontinued RYBREVANT due to IRR.

RYBREVANT as a Single Agent

In CHRYSALIS (n=302), IRR occurred in 66% of patients treated with RYBREVANT. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT due to IRR.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended. Administer RYBREVANT via a peripheral line on Week 1 and Week 2 to reduce the risk of infusion-related reactions. Monitor patients for signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity. If an anaphylactic reaction occurs, permanently discontinue RYBREVANT.

Interstitial Lung Disease/Pneumonitis

RYBREVANT can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.

RYBREVANT with LAZCLUZE

In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients treated with RYBREVANT in combination with LAZCLUZE, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case (0.2%) of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT and LAZCLUZE due to ILD/pneumonitis.

RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population, ILD/pneumonitis occurred in 2.1% treated with RYBREVANT in combination with carboplatin and pemetrexed with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% discontinued RYBREVANT due to ILD/pneumonitis.

RYBREVANT as a Single Agent

In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). For patients receiving RYBREVANT in combination with LAZCLUZE, immediately withhold both drugs in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. For patients receiving RYBREVANT as a single agent or in combination with carboplatin and pemetrexed, immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Venous Thromboembolic (VTE) Events with Concomitant Use of RYBREVANT and LAZCLUZE

RYBREVANT in combination with LAZCLUZE can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. The majority of these events occurred during the first four months of therapy.

In MARIPOSA, VTEs occurred in 36% of patients receiving RYBREVANT in combination with LAZCLUZE, including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE; 1% of patients had VTE leading to dose reductions of RYBREVANT, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE. The median time to onset of VTEs was 84 days (range: 6 to 777).

Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended. Monitor for signs and symptoms of VTE events and treat as medically appropriate.

Withhold RYBREVANT and LAZCLUZE based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT and LAZCLUZE at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT and continue treatment with LAZCLUZE at the same dose level at the discretion of the healthcare provider.

Dermatologic Adverse Reactions

RYBREVANT can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry skin.

RYBREVANT with LAZCLUZE

In MARIPOSA, rash occurred in 86% of patients treated with RYBREVANT in combination with LAZCLUZE, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT and 30% for LAZCLUZE, rash leading to dose reductions occurred in 23% of patients for RYBREVANT and 19% for LAZCLUZE, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT and 1.7% for LAZCLUZE.

RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population, rash occurred in 82% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT and 3.1% discontinued pemetrexed.

RYBREVANT as a Single Agent

In CHRYSALIS, rash occurred in 74% of patients treated with RYBREVANT as a single agent, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients.

Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT as a single agent.

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT or LAZCLUZE in combination with RYBREVANT. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free) emollient cream is recommended for dry skin.

When initiating RYBREVANT treatment with or without LAZCLUZE, administer alcohol-free emollient cream to reduce the risk of dermatologic adverse reactions. Consider prophylactic measures (e.g. use of oral antibiotics) to reduce the risk of dermatologic reactions. If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT in combination with LAZCLUZE, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity

RYBREVANT can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus, and uveitis.

RYBREVANT with LAZCLUZE

In MARIPOSA, ocular toxicity occurred in 16% of patients treated with RYBREVANT in combination with LAZCLUZE, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT and continue LAZCLUZE based on severity.

RYBREVANT with Carboplatin and Pemetrexed

Based on the pooled safety population, ocular toxicity occurred in 16% of patients treated with RYBREVANT in combination with carboplatin and pemetrexed. All events were Grade 1 or 2.

RYBREVANT as a Single Agent

In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT. All events were Grade 1-2.

Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose, or permanently discontinue RYBREVANT based on severity.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal models, RYBREVANT and LAZCLUZE can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus.

Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT.

Advise females of reproductive potential to use effective contraception during treatment with LAZCLUZE and for 3 weeks after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with LAZCLUZE and for 3 weeks after the last dose.

Adverse Reactions

RYBREVANT with LAZCLUZE

For the 421 patients in the MARIPOSA clinical trial who received RYBREVANT in combination with LAZCLUZE, the most common adverse reactions (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (RYBREVANT, 63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), nausea (21%), and ocular toxicity (16%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%).

Serious adverse reactions occurred in 49% of patients who received RYBREVANT in combination with LAZCLUZE. Serious adverse reactions occurring in ≥2% of patients included VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and infusion-related reaction (RYBREVANT) (2.1% each). Fatal adverse reactions occurred in 7% of patients who received RYBREVANT in combination with LAZCLUZE due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).

RYBREVANT with Carboplatin and Pemetrexed

For the 130 patients in the MARIPOSA-2 clinical trial who received RYBREVANT in combination with carboplatin and pemetrexed, the most common adverse reactions (≥20%) were rash (72%), infusion-related reactions (59%), fatigue (51%), nail toxicity (45%), nausea (45%), constipation (39%), edema (36%), stomatitis (35%), decreased appetite (31%), musculoskeletal pain (30%), vomiting (25%), and COVID-19 (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased neutrophils (49%), decreased white blood cells (42%), decreased lymphocytes (28%), decreased platelets (17%), decreased hemoglobin (12%), decreased potassium (11%), decreased sodium (11%), increased alanine aminotransferase (3.9%), decreased albumin (3.8%), and increased gamma-glutamyl transferase (3.1%).

In MARIPOSA-2, serious adverse reactions occurred in 32% of patients who received RYBREVANT in combination with carboplatin and pemetrexed. Serious adverse reactions in >2% of patients included dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and pulmonary embolism (2.3%). Fatal adverse reactions occurred in 2.3% of patients who received RYBREVANT in combination with carboplatin and pemetrexed; these included respiratory failure, sepsis, and ventricular fibrillation (0.8% each).

For the 151 patients in the PAPILLON clinical trial who received RYBREVANT in combination with carboplatin and pemetrexed, the most common adverse reactions (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), infusion-related reaction (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%).

In PAPILLON, serious adverse reactions occurred in 37% of patients who received RYBREVANT in combination with carboplatin and pemetrexed. Serious adverse reactions in ≥2% of patients included rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified.

RYBREVANT as a Single Agent

For the 129 patients in the CHRYSALIS clinical trial who received RYBREVANT as a single agent, the most common adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).

Serious adverse reactions occurred in 30% of patients who received RYBREVANT. Serious adverse reactions in ≥2% of patients included pulmonary embolism, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death.

LAZCLUZE Drug Interactions

Avoid concomitant use of LAZCLUZE with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.

Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.

Please read full Prescribing Information for RYBREVANT.

Please read full Prescribing Information for LAZCLUZE.

On March 26, 2025 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the Company will participate in the 24th Annual Needham Healthcare Conference. Company management will participate in a fireside chat on Wednesday, April 9, 2025, at 9:45 a.m. PT / 12:45 p.m. ET / 5:45 p.m. IST (Press release, Jazz Pharmaceuticals, MAR 26, 2025, View Source [SID1234651477]).

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An audio webcast of the fireside chat will be available via the Investors section of the Jazz Pharmaceuticals website at View Source A replay of the webcasts will be archived on the website for 30 days.

On March 26, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that preclinical data on multiple novel bispecific antibodies as well as antibody-drug-conjugates (ADCs) from its oncology pipeline will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Innovent Biologics, MAR 26, 2025, View Source [SID1234651476]). The AACR (Free AACR Whitepaper) Annual Meeting will take place from April 25 to April 30, 2025, in Chicago, Illinois.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Late-Breaking Research: Immunology 2

Topic: Preclinical Data of IAR037, A Novel CD40/PD-L1 Bispecific Antibody for the Treatment of Advanced Solid Tumors Resistant to Immune Checkpoint Inhibitors
Abstract Number: LB139
Presentation Time：Monday Apr 28, 2025 9:00 AM – 12:00 PM
Location: Poster Section 52

Late-Breaking Research: Clinical Research 1

Topic: Preclinical characterization of IBI3010, a FRα targeting biparatopic antibody-drug conjugate (ADC), for the treatment of FRα expressing tumors
Abstract Number: LB222
Presentation Time：Monday Apr 28, 2025 2:00 PM – 5:00 PM
Location: Poster Section 53

Poster Session: Experimental and Molecular Therapeutics – New and Emerging Cancer Drug Targets

Topic: IBI3019, a first-in-class EGFR/CDH17/CD16A tri-specific antibody, demonstrated potent efficacy against CRC and an excellent safety profile in preclinical studies
Abstract Number: 4249
Presentation Time: Tuesday Apr 29, 2025 9:00 AM – 12:00 PM
Location: Poster Section 17
Poster Board Number: 6

Poster Session: Experimental and Molecular Therapeutics – Therapeutic Approaches to Attack the Tumor Microenvironment

Topic: IBI3026, a first-in-class anti-PD-1/IL-12 fusion protein, demonstrates the potential to be a new immuno-oncology therapy by releasing the break in immune response and strongly activating T and NK cells in the tumor microenvironment
Abstract Number: 3118
Presentation Time: Monday Apr 28, 2025 2:00 PM – 5:00 PM
Location: Poster Section 24
Poster Board Number: 2

Poster Session: Experimental and Molecular Therapeutics – Biochemical Modulators of Cancer / Differentiation Therapeutic Strategies

Topic: IBI3014, a TROP2xPD-L1 bi-specific ADC integrating ADC killing with checkpoint blockade within one molecule, exhibits promising efficacy and safety in preclinical models
Abstract Number: 344
Presentation Time: Sunday Apr 27, 2025 2:00 PM – 5:00 PM
Location: Poster Section 16
Poster Board Number: 11

Poster Session: Experimental and Molecular Therapeutics – Biochemical Modulators of Cancer / Differentiation Therapeutic Strategies

Topic: Trop2 and B7H4 bi-specific ADC with improved efficacy and safety for gynecologic cancers
Abstract Number: 345
Presentation Time: Sunday Apr 27, 2025 2:00 PM – 5:00 PM
Location: Poster Section 16
Poster Board Number: 12

Poster Session: Immunology – T Cell Engagers

Topic: A 2+1 format MUC16 targeting T cell engager induces MUC16-dependent T cell activity and superior anti-tumor efficacy
Abstract Number: 3510
Presentation Time: Monday Apr 28, 2025 2:00 PM – 5:00 PM
Location: Poster Section 38
Poster Board Number: 18

Poster Session: Immunology – Modulation of Tumor Microenvironment: Modulation of Lymphocyte Influx

Topic: A PD1-IFNα fusion protein, composed of an attenuated IFNα fused to a clinically validated PD1 mAb, induced PD1-dependent IFNα signaling and demonstrated superior anti-tumor efficacy
Abstract Number: 4881
Presentation Time: Tuesday Apr 29, 2025 9:00 AM – 12:00 PM
Location: Poster Section 40
Poster Board Number: 9

Poster Session: Experimental and Molecular Therapeutics – Novel Antitumor Agents 3

Topic: Olverembatinib* (HQP1351) in combination with lisaftoclax (APG-2575) overcomes venetoclax resistance in preclinical models of acute myeloid leukemia (AML)
Abstract Number: 5652
Presentation Time: Tuesday Apr 29, 2025 2:00 PM – 5:00 PM

Poster Session: Experimental and Molecular Therapeutics – Novel Antitumor Agents 3

Topic: Effects of olverembatinib* (HQP1351) in combination with BCL-2 inhibitor lisaftoclax (APG-2575) in T-cell acute lymphoblastic leukemia (T ALL)
Abstract Number: 5648
Presentation Time: Tuesday Apr 29, 2025 2:00 PM – 5:00 PM

* In July 2021, Innovent and Ascentage Pharma (6855.HK) reached the agreement regarding the joint development and commercialization of olverembatinib in China.

Dr. Kaijie He, Vice President of Innovent, stated: "With the expansion and enhancement of Innovent Academy’s technology platforms, our global R&D efforts are taking shape and accelerating global competitiveness, enabling the efficient generation of novel molecules with global potential. We are proud to showcase a batch of preclinical research findings at this year’s AACR (Free AACR Whitepaper) Annual Meeting, including multiple globally first-in-class bispecific antibodies, multi-specific antibodies, and antibody-drug conjugates (ADCs). These breakthroughs not only demonstrate our growing scientific capabilities but also reaffirm our commitment to delivering transformative therapeutic options for patients worldwide. Moving forward, we remain focused on innovation—optimizing precision targets and exploring novel mechanisms—to provide revolutionary solutions for some of the world’s most challenging diseases and enable more patients to benefit from the rapid advancements in cutting-edge science."

On March 26, 2025 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported final survival data from a phase 2a clinical trial of CAN-2409 in patients with stage III/IV NSCLC, inadequately responding to ICI treatment (Press release, Candel Therapeutics, MAR 26, 2025, View Source [SID1234651475]). mOS was 24.5 months in 46 evaluable patients receiving 2 courses of CAN-2409 (per protocol population; cohort 1 and 2) and 21.5 months in evaluable patients from cohort 2 (n=41) that presented with progressive disease at baseline, despite ICI treatment. mOS in patients with progressive disease despite ICI treatment, was 9.8-11.8 months in other studies, including those with standard of care of docetaxel chemotherapy, which has a very poor prognosis, did not exceed 12 months in other published studies.(1, 2) This final analysis included extended follow-up data (1 year after the previous data cut) with a median follow up time for the per protocol population of 32.4 months. Data showed a sizable percentage of patients with survival exceeding 24 months, evidence of a long tail of survival, with 37% of patients with progressive disease despite treatment with ICI alive 2 years after CAN-2409 administration.

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Biomarker research showed an enhanced immunological and clinical response after CAN-2409 administration in patients with non-squamous histology compared to squamous histology, and improved mOS was observed in this population (25.4 months in patients with progressive disease despite ICI treatment and non-squamous NSCLC, n=33).

"Treatment options are quite limited for patients with unresectable NSCLC who progress on anti-PD-1 therapy," said Charu Aggarwal, MD, MPH, Leslye Heisler Professor for Lung Cancer Excellence at the University of Pennsylvania’s Perelman School of Medicine and Principal Investigator of the study. "The survival benefit seen in this study is striking, especially when compared to both the current standard of care treatment of docetaxel chemotherapy and other therapies under investigation for this patient group," she added.

Data Highlights:

Pre-treatment and mid-treatment dropout rates were comparable to those reported in other clinical trials in similar populations of patients with advanced NSCLC.(1, 3) Three patients were enrolled, but did not receive treatment, 22 patients received only one injection of CAN-2409, 51 patients received at least 2 injections of CAN-2409, but 5 patients did not complete treatment. 46 patients received complete treatment (2 courses of CAN-2409 plus prodrug) and were included in the evaluable, per protocol population. The per protocol population was representative of the overall enrolled population in terms of baseline demographics and prognostic factors.

Survival data:
In patients with an inadequate response to ICI treatment (Cohort 1+2, n=46), mOS was 24.5 months.
In patients with progressive disease, despite ICI treatment (Cohort 2, n=41), mOS was 21.5 months, which is markedly longer than the 9.8–11.8 months of survival reported in published literature in a similar patient population receiving standard of care of docetaxel chemotherapy.1,2
37% of patients exceeding 24 months survival were still alive at the time of the March 3, 2025 data cut.
Potential precision medicine approach:
Patients with non-squamous histology predominated amongst the long-term survivors: 14/15 patients with OS > 24 months and 9/9 patients with OS > 30 months had non-squamous NSCLC.
Patients with non-squamous histology exhibited larger changes in T cells, B cells, and dendritic cells after CAN-2409 administration compared to patients with squamous NSCLC.
mOS of 25.4 months observed in non-squamous NSCLC patients with progressive disease, despite ICI treatment (n=33).
Although a phase 2a open-label experimental medicine clinical trial is not designed for an intention to treat (ITT) analysis, we conducted an exploratory ITT analysis and observed mOS of 16.7 months after CAN-2409 administration in non-squamous NSCLC patients with progressive disease despite ICI treatment (n=53). Recent trials have reported a mOS of 9.9–12.3 months in ICI-refractory, non-squamous NSCLC patients receiving standard of care docetaxel chemotherapy.(1,2)
Systemic anti-tumor response (abscopal effect) and safety profile:
Decrease in size of uninjected tumors was observed in 69% of patients with multiple lesions (n=35), indicating that local injection may induce a systemic anti-tumor immune response (abscopal effect).
CAN-2409 maintained its generally favorable safety and tolerability profile throughout the extended follow-up period.
"These updated survival data confirm and strengthen our previously reported findings, demonstrating that CAN-2409 has the potential to extend survival for patients with advanced NSCLC, who have limited treatment options after failing to respond to, or progressing, despite immune checkpoint inhibitor therapy," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "CAN-2409 may represent an entirely new approach to solid tumor treatment, with its unique mechanism of action and favorable safety profile to date, enabling potentially meaningful improvements in outcomes beyond current standard of care. These compelling results mark a potentially transformative advance in our fight against this aggressive disease."

"The extension of survival in patients with non-squamous disease is notable even when compared to data that have been reported for other investigational products, such as antibody-drug conjugates, for this patient population," said W. Garrett Nichols, MD, CMO of Candel. "CAN-2409, in addition to continued ICI treatment, may prolong survival beyond that offered by docetaxel chemotherapy, and has the potential to be better tolerated."

Based on these positive findings, the Company will advance its development program for CAN-2409 in NSCLC, including preparation and enabling work for a future, potentially registrational, clinical trial in patients with NSCLC with non-squamous histology. The U.S. Food and Drug Administration (FDA) previously granted Fast Track Designation for CAN-2409 plus valacyclovir in combination with ICI treatment for the treatment of stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy.

About CAN-2409

CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus engineered to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the tumor. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic nucleotide analogue that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in-situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity, as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors, have previously been shown in several preclinical and clinical settings. More than 1,000 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies.

Candel’s clinical development program for CAN-2409 includes completed phase 2a clinical trials in both non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC), as well as a positive pivotal randomized, placebo-controlled phase 3 clinical trial of CAN-2409 in localized, non-metastatic prostate cancer. In December 2024, Candel announced that CAN-2409 achieved its primary endpoint in a phase 3 clinical trial in men with intermediate-to-high-risk, localized prostate cancer, demonstrating statistically significant and clinically meaningful improvement in disease-free survival when added to SoC radiation therapy +/- androgen deprivation therapy. In the Company’s randomized controlled phase 2a clinical trial of CAN-2409 in borderline resectable PDAC, positive survival data showed notable improvement in estimated median overall survival of 31.4 months after experimental treatment with CAN-2409 plus standard of care versus 12.5 months in the control group in patients with PDAC, who received only standard of care. Median survival post-progression was 21.2 months in patients who received CAN-2409 compared to 6.4 months in the control arm. CAN-2409 plus prodrug has been granted Fast Track Designation by the FDA for the treatment of PDAC, stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy, and localized primary prostate cancer. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC. Candel’s pivotal phase 3 clinical trial in newly diagnosed, localized prostate cancer was conducted under a Special Protocol Assessment (SPA) agreed with the FDA.