20 Lung Cancer Companies Advancing New Treatments in 2025
- Guru Singh
- May 28
- 27 min read
Updated: Jun 3
Lung cancer remains the leading cause of cancer-related deaths worldwide. However, a new wave of therapies is expanding options for patients, driven by personalized medicine and innovative science. New treatments for lung cancer include a growing number of targeted therapies and new forms of immunotherapy, according to leading oncologists at major cancer centers. Many emerging drugs are tailored to specific genetic or protein biomarkers, while others train or enhance the immune system to attack tumors.
Combination approaches are also on the rise, pairing modalities like immunotherapy with targeted drugs or even medical devices to improve outcomes. Artificial intelligence and advanced genomic tools, supported by platforms like Scispot that help biotech companies accelerate R&D through intelligent automation, are helping discover novel targets, contributing to an accelerating pipeline of lung cancer therapeutics. These trends reflect in the global lung cancer therapeutics market, which is expected to grow from $37.5 billion in 2024 to $112.8 billion by 2034.
Innovative startups and biotech companies around the world are developing next-generation treatments from cancer vaccines and oncolytic viruses to bispecific antibodies, gene therapies, and precision small molecules. Many are pursuing regulatory approvals or pivotal trial readouts in 2025 and beyond.
Below, we profile 20 cutting-edge lung cancer biotech companies spanning early-stage to near-commercial across North America, Europe, and Asia advancing new treatment options. For each, we highlight their platform technology, lead candidate, recent clinical news, upcoming milestones, financial status, and what differentiates their approach from existing therapies.
Technology: Viral immunotherapy (oncolytic virus-based vaccine)
Lead Lung Cancer Candidate: CAN-2409
Recent News: Reported positive Phase 2a survival data for CAN-2409 in advanced NSCLC
Candel Therapeutics is developing oncolytic viral immunotherapies that provoke a patient's immune system to recognize and destroy tumors. Its lead candidate CAN-2409 is an engineered adenovirus that delivers the HSV-tk gene into tumor cells, priming them for destruction.
After intratumoral injection of CAN-2409, patients receive the antiviral prodrug valacyclovir, which the introduced HSV-tk enzyme converts into a toxic nucleotide analog inside infected cancer cells. This process kills tumor cells and releases antigens, inducing a systemic anti-tumor T-cell response against the primary tumor and any metastases.
In a Phase 2a trial for non-small cell lung cancer (NSCLC), CAN-2409 showed encouraging efficacy for patients with advanced disease who had failed prior therapies. Treated patients achieved a median overall survival of 24.5 months despite having progressed after multiple lines of chemotherapy and immunotherapy.
Importantly, CAN-2409 demonstrated activity in both squamous and non-squamous NSCLC, persuading the company to pursue non-squamous NSCLC in its next trial. Candel is now planning a registrational trial in lung cancer, leveraging these results. The approach is differentiated by its localized delivery and by turning the tumor into a vaccine factory, potentially effective even when checkpoint inhibitors failed, by rekindling immune responses.
On the financial front, Candel bolstered its cash reserves with a $92 million public offering in late 2024, funding ongoing trials and a planned Biologics License Application (BLA) submission for CAN-2409 in another indication (prostate cancer). This strong financial position supports the company's next steps in lung cancer, where CAN-2409 could offer a novel immunotherapy option for difficult, treatment-resistant cases.
Technology: Targeted therapy (EGFR exon 20 insertion inhibitor)
Lead Lung Cancer Candidate: Zipalertinib (CLN-081/TAS6417)
Recent News: Phase 2b trial in EGFR exon 20 insertion NSCLC met its primary endpoint (objective response rate)
Cullinan Therapeutics is developing precision oncology drugs and recently scored success with zipalertinib, a next-generation EGFR exon 20 insertion inhibitor for NSCLC. EGFR exon20 insertion mutations are an elusive target. They account for up to 4% of NSCLC, making them the third most common EGFR subtype, but are poorly served by first-generation EGFR inhibitors.
Zipalertinib is a potent oral small molecule designed to selectively target EGFR exon20ins mutants while sparing wild-type EGFR, thereby attacking this resistant mutation with hopefully fewer side effects. In collaboration with Taiho Pharmaceutical in Japan, Cullinan tested zipalertinib in a Phase 2b trial for NSCLC patients harboring EGFR exon20 insertions who had received prior therapy.
The trial met its primary endpoint, achieving a robust overall response rate (ORR) in this refractory patient population. While full data will be presented at ASCO 2025, the companies noted results were consistent with earlier findings. Previously at ESMO Congress, zipalertinib showed an ORR of approximately 40% with a manageable safety profile in patients who had even progressed on amivantamab (an FDA-approved exon20-targeted antibody).
This signals that zipalertinib can produce significant tumor regressions in a setting where few options exist, differentiating it from older EGFR inhibitors like osimertinib which have minimal activity against exon20 insertion mutations. Cullinan is expected to advance zipalertinib into a registrational program, buoyed by these results.
The company is well-funded: in April 2024, it raised $280 million in a private placement to support ongoing R&D. Upcoming milestones likely include detailed Phase 2b data at major conferences and potential regulatory discussions for accelerated approval, given the high unmet need. With zipalertinib, Cullinan aims to fill a critical gap for the 12% of EGFR-mutant NSCLC patients whose tumors have exon20 insertions, offering hope for a genetically defined subgroup with historically poor outcomes.
Technology: DNA-damaging chemotherapy (alkylating agent)
Lead Lung Cancer Drug: Zepzelca (lurbinectedin)
Recent News: Positive Phase 3 results for Zepzelca + Tecentriq as first-line maintenance in small cell lung cancer
Jazz Pharmaceuticals, though known for commercial products in oncology and neuroscience, is included here for its novel drug lurbinectedin (Zepzelca) in lung cancer. Zepzelca is an alkylating agent originally derived from a marine organism, which binds to DNA's guanine residues and disrupts transcription factors and DNA repair, leading to cancer cell death.
Jazz secured accelerated FDA approval in 2020 for Zepzelca to treat metastatic small cell lung cancer (SCLC) in second-line after platinum chemotherapy. This approval was based on a trial showing meaningful response rates in a disease with notoriously few treatment options.
To convert this to full approval, Jazz has been running two confirmatory Phase 3 trials. The first trial (called LAGOON) tested Zepzelca + atezolizumab (Tecentriq) vs. immunotherapy alone as a maintenance therapy after first-line chemo in extensive-stage SCLC. In late 2024, Jazz reported that the addition of Zepzelca significantly delayed progression and extended survival compared to Tecentriq alone.
In fact, the Zepzelca combo outperformed Tecentriq alone, delaying disease progression and extending survival, and Jazz announced plans to file for FDA approval of the combination in the first half of 2025. The second Phase 3 (called ATLANTIS) is testing Zepzelca (with or without chemo) versus physician's choice chemo in relapsed SCLC. If positive (completion expected in 2026), it could solidify Zepzelca's role and support full approval.
Jazz's strategy shows the increasing trend of combination therapies in solid tumors, pairing a DNA-targeting drug with immunotherapy to potentially trigger more tumor antigen release and immune recognition. Financially, Jazz remains strong, having executed an $850 million private offering in September 2024 (largely to refinance debt and fund corporate purposes).
What differentiates Zepzelca is that it's one of the few new agents active in SCLC, an area long dominated by decades-old chemotherapies. By improving outcomes in first-line maintenance, Zepzelca could become part of a new standard of care in SCLC, an important advance in a very aggressive cancer.
Technology: Targeted small molecule (telomere-targeting agent)
Lead Lung Cancer Candidate: THIO (6-thio-dG)
Recent News: Reported Phase 2 efficacy (16.9-month median OS in advanced NSCLC) and preparing Phase 3 start in late 2025
MAIA Biotechnology is a small-cap company taking a unique route in lung cancer: targeting telomeres, the protective DNA sequences at chromosome ends. Their lead molecule THIO (aka 6-thio-2′-deoxyguanosine) is a telomere-interfering agent. It is selectively recognized by the enzyme telomerase, which is highly active in cancer cells (enabling them to bypass normal aging).
When THIO is incorporated into telomeres by telomerase, it causes dysfunctional telomere structures and essentially "uncaps" the chromosome ends. This leads to genomic instability and rapid tumor cell death. In effect, MAIA is weaponizing telomerase against cancer, a mechanism quite distinct from standard chemotherapy.
THIO is being tested in combination with immunotherapy. Preclinical models showed that a low dose of THIO given before a PD-1/PD-L1 inhibitor could completely eliminate advanced tumors and even establish immune memory to prevent recurrence. This is thought to happen because THIO-induced tumor cell death releases neoantigens and creates an inflamed tumor microenvironment, making previously "cold" tumors responsive to checkpoint inhibitors.
In a Phase 2 trial (THIO-101) for advanced NSCLC patients who failed multiple prior treatments, MAIA evaluated THIO followed by cemiplimab (Libtayo, a PD-1 inhibitor). In early 2025, the company announced encouraging results: third-line NSCLC patients who received at least one THIO dose had a median overall survival of 16.9 months, which is notable in this refractory setting.
Based on this, MAIA is planning to initiate a Phase 3 trial in the second half of 2025 to confirm THIO's benefit in checkpoint inhibitor-resistant NSCLC. The Phase 3 will evaluate THIO plus an immune checkpoint inhibitor in a similar population, aiming to establish a new option for immunotherapy-relapsed patients.
MAIA's resources, while modest, have been buoyed by recent funding. In late 2024, it raised about $0.95 million, followed by another $1.08 million private placement in early 2025. The company also secured non-dilutive grant support.
THIO's competitive edge is its novel mechanism: by targeting telomeres, it attacks a vulnerability shared by most cancer cells (telomerase dependence), and it synergizes with immunotherapy in a way that could rescue patients who no longer respond to PD-1/L1 inhibitors. If successful, THIO would represent the first telomere-targeted treatment in oncology and open a new front in the fight against lung cancer.
Technologies: Precision kinase inhibitors for ROS1, ALK, and HER2 mutations
Lead Candidate: Zidesamtinib (NVL-520, ROS1 inhibitor)
Recent News: Closed a $575 million upsized public offering to fund pivotal trials; expects first pivotal ROS1 data in 1H 2025
Nuvalent is a U.S.-based biotech building a pipeline of targeted therapies for genetically defined lung cancers. It has three parallel programs: one targeting ROS1 fusion-positive NSCLC, one targeting ALK fusion-positive NSCLC, and one for cancers with HER2 mutations.
Nuvalent's lead is zidesamtinib (NVL-520), a brain-penetrant ROS1 tyrosine kinase inhibitor (TKI). ROS1 fusions drive approximately 1-3% of NSCLC cases, but patients eventually develop resistance to existing ROS1 TKIs (like crizotinib or entrectinib), often via mutations like ROS1 G2032R or via brain metastases (as many TKIs have limited CNS activity).
Zidesamtinib was rationally designed to tackle these issues. It can inhibit ROS1 fusion proteins even with resistance mutations and is engineered to cross the blood-brain barrier. Nuvalent recently transitioned its first-in-human trial of zidesamtinib into the Phase 2 pivotal stage. In late 2023, they dosed ROS1-positive NSCLC patients who had been pre-treated with ROS1 TKIs in the expansion cohort.
The company guided that pivotal data for NVL-520 are expected in the first half of 2025, focusing on patients who have already received TKIs. Nuvalent is aiming to show sufficient efficacy to support an initial New Drug Application (NDA) for ROS1-positive NSCLC by mid-2025. Notably, zidesamtinib could address a high unmet need if it shows robust activity against ROS1 resistance mutations and brain mets, setting it apart from earlier drugs.
Alongside, Nuvalent's second candidate neladalkib (NVL-655) is a next-generation ALK inhibitor currently in Phase 1/2. It likewise is meant for ALK-positive NSCLC that has become resistant to first-, second-, or even third-generation ALK TKIs (like crizotinib, ceritinib, lorlatinib). The Phase 2 expansion for NVL-655 began in Feb 2024, and Nuvalent anticipates reporting pivotal ALK inhibitor-pretreated patient data by end of 2025. The third program targeting HER2 mutant lung cancer is in earlier stages.
Nuvalent's execution has been bolstered by significant funding. After a $135 million Series B in 2021 and a successful IPO the same year, Nuvalent raised an impressive $575 million in an upsized public equity offering in 2023. This gives it the financial firepower to carry multiple lung cancer programs through expensive late-phase trials.
The company's competitive differentiation is its focus on "next-generation" targeted TKIs that tackle resistance and CNS penetration from the outset. If zidesamtinib and neladalkib deliver on their promise, Nuvalent could bring forward best-in-class targeted options for ROS1 and ALK-driven NSCLC, potentially resetting the standard of care for patients who progress on current TKIs.
Technology: HER2-targeted immunotherapy (Listeria-based cancer vaccine)
Lead Candidate: OST-HER2 (OST-31-164)
Recent News: Phase 2b in osteosarcoma lung metastases hit primary endpoint; 33% of patients recurrence-free at 1 year; seeking FDA accelerated approval pathway
OS Therapies is taking an unconventional path in the lung cancer space by targeting metastatic osteosarcoma that has spread to the lungs. Its therapy, OST-HER2, is a novel cancer vaccine that uses a genetically modified Listeria monocytogenes bacterium to stimulate immunity against HER2-expressing cancer cells.
While HER2 is often associated with breast cancer, it's also expressed in osteosarcoma and some lung cancers. OST-HER2's premise is to infect the patient with a safe, attenuated Listeria that presents HER2 fragments, thereby training the immune system (T-cells) to hunt down and destroy HER2-positive tumor cells wherever they reside.
In a Phase 2b trial, OS Therapies targeted a very specific yet dire scenario: recurrent osteosarcoma that metastasized to the lungs, after surgical removal of visible tumors. For these young patients, preventing recurrence is critical. The study showed that 33% of patients remained relapse-free at 12 months after OST-HER2 treatment, a notable result in this aggressive disease.
Moreover, early data indicated improved overall survival: at 1 year, survival was 91% with OST-HER2 vs. approximately 80% in matched historical controls, and at 2 years 61% vs. 40%. These promising results suggest the immunotherapy may be effectively clearing micrometastatic disease in the lungs.
On the strength of this data, OS Therapies' CEO stated they will pursue an FDA accelerated approval for OST-HER2. The plan is to present the Phase 2b outcomes to the FDA and argue that OST-HER2 addresses a high unmet need (no approved therapies specifically prevent osteosarcoma lung metastasis recurrence).
To fund operations, OS Therapies closed a $6 million private placement in Dec 2024, which is expected to sustain the company into 2026. By that time, they aim to have regulatory approval and possibly launch commercialization of OST-HER2 in the U.S.
What makes OST-HER2 stand out is its use of a live bacterial vector to generate a potent immune response in a setting where traditional chemo or targeted drugs have limited efficacy. It also represents the broader trend of therapeutic cancer vaccines making a comeback, using new strategies to overcome tumors' immune evasion.
If approved, OST-HER2 would be one of the first adjuvant immunotherapies in osteosarcoma and a proof-of-concept for Listeria-based vaccines in solid tumors (an approach that could be expanded to more common lung cancers expressing HER2 or other antigens).
Technology: Bispecific antibody (PD-1 × VEGF dual blockade)
Lead Candidate: Ivonescimab (aka AK112, brand name in China: Symbering)
Recent News: Posted three positive Phase 3 trials in NSCLC; in 2024, outperformed Keytruda in PD-L1+ NSCLC (49% lower risk of progression/death) and hit PFS endpoint in squamous NSCLC chemo combo; China approved ivonescimab + chemo for EGFR-mutant NSCLC
Summit Therapeutics, in partnership with China-based Akeso Inc., is developing ivonescimab, a first-in-class bispecific antibody that targets both PD-1 (an immune checkpoint) and VEGF (a key factor in tumor angiogenesis). By combining these mechanisms in a single molecule, ivonescimab aims to unleash an immune attack on the cancer while also cutting off its blood supply.
This dual action could be synergistic: PD-1 blockade activates T-cells, and anti-VEGF normalizes tumor vessels and counteracts immunosuppression in the tumor microenvironment. Ivonescimab has generated considerable excitement with its trial results.
In 2024, it was approved in China (branded Symbering) for NSCLC patients with EGFR-mutated tumors, in combination with chemotherapy, after EGFR TKI failure. This made it the first immunotherapy indicated specifically for EGFR-mutant lung cancer in that setting.
Under Summit's purview (which licensed rights for U.S., EU, Japan and others), multiple global Phase 3 trials are ongoing or recently read out positive:
One trial in PD-L1 positive advanced NSCLC (first-line) showed ivonescimab plus chemo significantly beat standard-of-care pembrolizumab (Keytruda) plus chemo. Data presented in 2024 indicated ivonescimab's regimen slashed the risk of disease progression or death by 49% compared to Keytruda's. In other words, ivonescimab was more effective than the market-leading PD-1 inhibitor in that subset, a remarkable feat suggesting the PD-1×VEGF combo has added benefit.
Another Phase 3 (the SHIELD-1 study) in first-line squamous NSCLC (both PD-L1 positive and negative) testing ivonescimab + chemo vs chemo alone met its primary endpoint in April 2025. The combination significantly improved progression-free survival for both PD-L1(+) and PD-L1(-) patients and had a favorable safety profile. This marked the third successful Phase 3 trial for ivonescimab in lung cancer, underscoring its broad potential.
Given these results, ivonescimab appears poised to become a breakthrough immunotherapy in lung cancer. Summit is actively collaborating with regulators to bring ivonescimab to Western markets, and has also teamed up with Pfizer to explore it with various antibody-drug conjugates (ADCs) in solid tumors, a sign of its perceived versatility.
Summit's financials were boosted by a $500 million licensing upfront from Akeso in 2022 and by a $235 million private placement in Sept 2024, ensuring funds to execute Phase 3 programs.
In a crowded immunotherapy field, ivonescimab's competitive edge lies in its dual targeting strategy, which no approved lung cancer drug currently employs. It offers the convenience of one antibody doing the job of two drugs (an anti-PD-1 and an anti-VEGF), potentially with an improved efficacy and safety profile. If Summit secures approvals, ivonescimab could become a new cornerstone therapy, especially for patients (like EGFR-mutant or squamous NSCLC) who haven't benefited as much from first-generation immunotherapies.
Technology: Gene therapy (tumor-suppressor gene delivery)
Lead Candidate: Reqorsa (quaratusugene ozeplasmid, TUSC2 gene therapy)
Recent News: Positive interim results from two Phase 1/2 trials (Acclaim-1 and -3) combining Reqorsa with Tagrisso and immunotherapy; Fast Track and Orphan designations in NSCLC; launched additional trials in SCLC
Genprex is pioneering a novel gene therapy approach to lung cancer. Its lead candidate, Reqorsa, delivers the TUSC2 tumor suppressor gene encapsulated in a nanoparticle lipid vector to patients' tumor cells. TUSC2 is a gene that is often lost or underexpressed in lung cancers; restoring it can promote cancer cell death and sensitivity to other treatments.
Reqorsa is administered intravenously and the nanoparticles naturally home to the lungs, making it especially suited for lung tumors. Genprex is running multiple trials under the "Acclaim" series to evaluate Reqorsa in different settings:
Acclaim-1: Reqorsa + osimertinib (Tagrisso) in EGFR-mutant NSCLC that progressed on Tagrisso.
Acclaim-2: Reqorsa + pembrolizumab (Keytruda) in late-line NSCLC.
Acclaim-3: Reqorsa + chemotherapy in extensive-stage small cell lung cancer (SCLC).
In mid-2024, Genprex announced promising preliminary efficacy from Acclaim-1 and Acclaim-3, while opting to discontinue Acclaim-2 (due to slow enrollment). In Acclaim-1 (Tagrisso combo), two of the first patients achieved notable long-term disease control: one patient had a partial response and remained progression-free for over 2 years on therapy, and another maintained stable disease for over 15 months.
These anecdotes hint that adding Reqorsa can re-sensitize some EGFR-mutant tumors to Tagrisso, potentially overcoming resistance. In Acclaim-3 (for SCLC), initial safety was acceptable, and the trial design is being presented at ASCO 2025, underscoring the novelty of gene therapy in SCLC.
Regulators have taken notice of Reqorsa's potential. The FDA granted Fast Track Designation for Reqorsa + Tagrisso in EGFR-mutant NSCLC, and an Orphan Drug Designation in SCLC, which will streamline development. Genprex has also received clearance to expand trials and is collaborating with academic centers to present new preclinical data (for instance, showing Reqorsa could help overcome KRAS inhibitor resistance).
Financially, Genprex is a smaller company but has managed to secure funding through public offerings and at-the-market sales. It's also benefitted from strategic research partnerships (with University of Texas MD Anderson, etc.). The upcoming milestones include completing enrollment in the Phase 2 portion of Acclaim-1 by late 2025 for an interim analysis, and advancing Acclaim-3 in SCLC.
Genprex's strategy is highly differentiated: rather than another drug targeting a protein, it delivers a missing gene directly to tumor cells. If successful, Reqorsa would become the first systemically administered gene therapy for cancer. Its ability to be combined with TKIs or immunotherapy opens a new combinatorial approach, effectively rewiring tumor biology to heighten responsiveness to standard treatments.
This could be paradigm-shifting for cases like EGFR inhibitor resistance, where options are limited beyond chemotherapy. Genprex, though early-stage, exemplifies how gene therapy can be applied to solid tumors like lung cancer, and 2025 will be a crucial year to watch its clinical progress.
Technology: Bispecific antibody (targets HER2 and HER3 signaling)
Lead Candidate: Zenocutuzumab (commercial name Bizengri)
Recent News: FDA accelerated approval granted (Dec 2024) for zenocutuzumab in NRG1 fusion-positive NSCLC and pancreatic cancer; first-in-class HER2×HER3 bispecific to reach market, with confirmatory trials ongoing
Merus, a biotech based in the Netherlands, has developed zenocutuzumab (ZNZ), a ground-breaking bispecific antibody that targets the HER3 receptor but is "armed" to block a unique driver of certain cancers: NRG1 gene fusions. NRG1 fusions are rare genomic events (found in <1% of lung cancers) where part of the NRG1 gene (which encodes a ligand for HER3) is aberrantly fused to another gene, leading to continuous activation of HER3-HER2 signaling and cancer growth.
Standard HER2 inhibitors don't work here because the cancer isn't overproducing HER2 itself; it's driven by the NRG1 fusion protein constantly activating HER3. Zenocutuzumab was intelligently designed with one arm binding to HER2 and another to HER3, latching the two receptors together in an inactive conformation, thereby preventing the NRG1 fusion from signaling.
On December 4, 2024, the FDA granted accelerated approval to zenocutuzumab (now branded Bizengri) for adults with advanced NSCLC (or pancreatic cancer) harboring NRG1 fusions. This milestone made Bizengri the first approved therapy for NRG1 fusion-positive lung cancer.
The decision was supported by clinical trial results in which zenocutuzumab produced durable tumor responses in a significant fraction of patients with chemo-refractory NRG1+ cancers. For instance, a patient-based real-world study and trial data showed meaningful response rates and prolonged disease control in this otherwise untreatable subgroup.
The significance is twofold: (1) it validates bispecific antibodies as a therapeutic class in solid tumors (Bizengri is noted as the first HER2×HER3 bispecific approved), and (2) it inaugurates treatment for a tumor-agnostic biomarker (NRG1 fusion) similar to how NTRK fusions or MSI-H have tissue-agnostic approvals.
Merus is now conducting a Phase 2 eXclaim trial as confirmatory study and will need to convert the accelerated approval to full approval by demonstrating clinical benefit (e.g., improved survival). In the meantime, Bizengri is available under the accelerated pathway for NRG1+ patients who often are desperate for options.
Merus's financial position is solid, with partnerships (like a multi-program deal with Lilly) and sufficient cash from past raises to fund operations. They received FDA Breakthrough Therapy designation earlier, expediting development, and are likely exploring broader indications for their bispecific platform.
What differentiates zenocutuzumab is its ultra-precision approach: it targets a fusion driver present in perhaps only a few hundred lung cancer patients per year. Traditional pharma often neglects such small populations, but Merus's success shows that innovative biotechs can make a viable medicine by focusing on the biology.
Key opinion leaders have hailed this as a win for the "long tail" of cancer genomics, using cutting-edge biologics to target even rare drivers. For lung cancer, it means that NRG1 fusion testing will become more important, and patients with this rare mutation now have a purpose-built therapy that can induce remissions where chemo and immunotherapy usually fail.
Technology: Targeted therapy (next-generation EGFR inhibitor for exon20 insertion mutations)
Lead Candidate: Sunvozertinib (DZD9008, China trade name: Delytact)
Recent News: Submitted NDA to U.S. FDA (Nov 2024) for sunvozertinib in EGFR exon20ins NSCLC; FDA granted Priority Review and Breakthrough Therapy designation, after China's approval made it the first oral drug for EGFR exon20ins NSCLC
Dizal, a biotech originating from China, has emerged as a global player with sunvozertinib, a potent oral inhibitor targeting EGFR exon 20 insertion mutations. EGFR exon20ins has been a notoriously tough target; it's a variant of EGFR that doesn't respond well to standard EGFR inhibitors like erlotinib or osimertinib.
Sunvozertinib was specifically crafted to covalently bind and inhibit these exon20-altered EGFR proteins with high selectivity, while sparing wild-type EGFR to reduce toxicity. Sunvozertinib achieved a major breakthrough in 2023 by securing approval in China, making it the world's first and only oral drug for NSCLC patients with EGFR exon20ins, initially for patients after chemotherapy.
This was based on impressive pivotal trial results. In the multicenter WU-KONG6 study for previously treated NSCLC, sunvozertinib demonstrated a confirmed ORR of around 44-53%, vastly outperforming historical chemo results. Moreover, in a frontline cohort, early data showed an ORR of 78.6% with median progression-free survival of 12.4 months on sunvozertinib, signaling potential as a first-line treatment.
Riding on this data, Dizal submitted a New Drug Application (NDA) in the U.S. in Nov 2024 for sunvozertinib in advanced NSCLC with EGFR exon20ins who have progressed after platinum chemo. The FDA granted Priority Review (with a PDUFA date expected in mid-2025) and earlier had conferred Breakthrough Therapy Designation for first-line use. These signal the FDA's recognition of sunvozertinib's potential to fill an unmet need.
If approved, it will directly compete with Janssen's amivantamab (an IV antibody approved for post-chemo exon20ins NSCLC) and Takeda's mobocertinib (an older small molecule that received accelerated approval but faced challenges). Sunvozertinib's advantages include being an oral pill with strong efficacy and possibly a better safety/tolerability profile; for instance, dose optimization led to reduced rash/diarrhea while maintaining activity.
Financially, Dizal has the backing of its listing on the Shanghai STAR market and a partnership with AstraZeneca (from which it was originally a joint venture). The company's cash infusion from the IPO and Chinese approval sales will support global expansion. They're also conducting trials in broader populations (e.g., first-line setting per the BTD scope).
Sunvozertinib's competitive differentiation is clear: it stands to become the standard of care for EGFR exon20ins-mutated NSCLC. By achieving deeper and more durable responses than prior attempts, it may extend survival for a subset of EGFR-mutant lung cancer patients who until recently had grim prospects.
Additionally, Dizal's success exemplifies the rise of Chinese biotechs on the world stage, innovating locally and then rapidly globalizing a medicine. The lung cancer field is watching closely, as sunvozertinib could supersede earlier exon20 drugs and even challenge chemotherapy + immunotherapy in relevant patients if moved to first-line.
Technology: mRNA cancer vaccine (personalized immunotherapy)
Lead Lung Cancer Program: BNT116 (FixVac for NSCLC) and BNT122 (iNeST personalized vaccine)
Recent News: Launched a first-in-world Phase 1 trial of BNT116 across 7 countries (2024) for advanced NSCLC; early data to be presented from BNT116 and BNT122 trials in 2025 as BioNTech expands into solid tumors
BioNTech, the German biotech famed for its COVID-19 vaccine, is leveraging its mRNA technology for lung cancer. Its BNT116 candidate is an off-the-shelf mRNA vaccine designed to encode multiple tumor-associated antigens common in NSCLC, thus boosting immune responses against the tumor.
In August 2024, BioNTech and academic collaborators kicked off a "world-first" trial of an mRNA lung cancer vaccine: the Phase 1/2 EmpowerLung 1 study of BNT116 in advanced NSCLC. This trial spans 34 sites in seven countries and involves about 130 patients, testing BNT116 in various settings from neoadjuvant to metastatic disease, often in combination with checkpoint inhibitors (e.g., cemiplimab).
The first patient was dosed in the UK in August 2024 amid optimism that mRNA vaccines could "hunt down and kill cancer cells then prevent them from coming back." BNT116 works by delivering mRNA instructions for certain NSCLC antigens into the patient's cells, which then produce those antigen fragments internally. This effectively trains the immune system to recognize and attack tumor cells carrying those antigens. The approach is similar to how COVID mRNA vaccines teach the immune system to target the spike protein.
For cancer, the goal is a potent T cell response against multiple tumor markers, ideally leading to tumor shrinkage and long-term immune memory. Additionally, BioNTech (with partner Genentech) is advancing BNT122 (autogene cevumeran), a fully personalized mRNA vaccine where a unique cocktail of up to 20 neoantigens is custom-made for each patient's tumor mutations.
BNT122 is in Phase 2 testing as an adjuvant therapy after surgery (notably in pancreatic cancer and likely soon in lung). Though not specific to lung, the first proof-of-concept of a personalized mRNA vaccine in melanoma (presented in late 2022) showed it cut relapse risk by approximately 44% when added to pembrolizumab. This has spurred BioNTech to initiate trials in lung cancer for the personalized vaccine approach as well.
Recent updates indicate BioNTech will present initial clinical data for BNT116 in 2025, perhaps early safety and immunogenicity findings. The company is also launching combination trials; for example, LuCa-MERIT-1 study testing BNT116 with docetaxel in checkpoint-refractory NSCLC, and plans to explore BNT116 alongside novel antibodies or ADCs.
BioNTech's financial strength is unquestionable after its COVID success (over $19 billion in revenue in 2021). It has funneled those resources into oncology R&D, with a broad slate of trials and even an AI collaboration to identify new targets.
In lung cancer specifically, BioNTech is positioning itself at the forefront of cancer vaccines, a field that is resurging due to technology breakthroughs. The competitive differentiation here is the mRNA platform: it allows rapid development and manufacturing of vaccines against cancer-specific antigens, including tailoring to an individual's tumor.
If BNT116 or BNT122 show strong efficacy, they could usher in a new era of personalized immunotherapy for lung cancer, potentially as an adjunct to surgery or checkpoint inhibitors to reduce relapse. The concept of using the body's own immune system, guided by mRNA blueprints, to seek and destroy lung cancer cells is a distinctly 21st-century modality, and BioNTech is leading that charge.
Technology: Nanoparticle radioenhancer (hafnium oxide) to amplify radiotherapy
Lead Lung Program: NBTXR3 (brand name in trials: JNJ-itegrity, a partnership with J&J) Recent News: Dosed first patient in a Phase 2 trial (CONVERGE) for stage III unresectable NSCLC in Q1 2025; Phase 1 results showed favorable safety and early efficacy when re-irradiating NSCLC with NBTXR3; extended cash runway to 2026 via J&J partnership amendment
Nanobiotix, a French biotech, is innovating a non-drug approach for solid tumors including lung cancer. Their product NBTXR3 is a radioenhancing nanoparticle: crystals of hafnium oxide administered by intratumoral injection. Hafnium is a heavy element that, when hit by X-ray radiation, releases a shower of electrons, thereby increasing DNA damage within cancer cells.
In simpler terms, NBTXR3 is like "tumor-targeted micro-dose of radiation amplifier"; it stays inside tumor tissue and makes standard radiotherapy far more lethal to that tumor, without increasing harm to healthy tissues. In 2020, NBTXR3 gained its first approval in Europe (for soft tissue sarcoma), and since then Nanobiotix has partnered with Johnson & Johnson (Janssen) to develop it in other cancers.
In lung cancer, radiotherapy is commonly used for unresectable Stage III NSCLC (in combination with chemotherapy), but cure rates are still low due to radioresistant cells. Nanobiotix is testing whether injecting NBTXR3 into the primary lung tumor can significantly improve outcomes.
The Phase 2 CONVERGE study in Stage III NSCLC started in early 2025, with J&J as sponsor, and the first patient was dosed in Q1 2025. This randomized trial evaluates NBTXR3 activated by radiotherapy versus radiotherapy alone in patients who cannot undergo surgery.
Parallelly, MD Anderson Cancer Center conducted a Phase 1 study for patients with locally recurrent NSCLC needing re-irradiation. At the 2025 European Lung Cancer Conference (ELCC), investigators presented data showing that radiotherapy + NBTXR3 had a favorable safety profile and signs of efficacy in these tough cases. Essentially, even heavily pre-treated lungs tolerated the nanoparticles and second radiation well, and some tumor control was observed.
This is significant because re-irradiating lung tissue is usually very risky; NBTXR3 might allow it with better effect and manageable safety. Financially, Nanobiotix secured an amended global licensing deal with J&J in 2025 that not only provided a cash infusion (J&J paid for certain development costs) but also extended Nanobiotix's cash runway into mid-2026.
The amendment reduced Nanobiotix's expense burden for the head & neck Phase 3 (their most advanced program) and preserved future milestone payouts. As of Q1 2025, Nanobiotix had €39.8 million in cash, with J&J committed to funding key trials, a strong position for a company of its size.
Nanobiotix's approach is unique among this list as it's not a molecule or biologic but a medical device plus drug hybrid (the particles are considered a drug-device combo). The competitive advantage is that NBTXR3 can potentially be added to any radiotherapy regimen to improve efficacy without changing systemic therapy.
For lung cancer, this could mean higher cure rates in stage III and the ability to re-treat or escalate dose safely. It exemplifies the trend of physical sciences in oncology, using physics and engineering to fight cancer. If Phase 2 and 3 trials confirm the early promise, NBTXR3 could become a widely adopted adjunct to radiation in lung cancer, transforming a century-old therapy (X-rays) into a more potent, targeted attack with minimal additional toxicity.
Technology: Targeted small molecule (covalent KRAS G12C inhibitor that binds active & inactive states)
Lead Candidate: BBO-8520
Recent News: Granted FDA Fast Track for BBO-8520 in previously treated KRAS G12C-mutant metastatic NSCLC; Phase 1 ongoing, preclinical data showed it binds KRAS G12C in both "ON" and "OFF" conformations, potentially overcoming resistance to first-gen KRAS inhibitors
BridgeBio Oncology, a spin-out from BridgeBio Pharma, is aiming to leapfrog current therapies for one of the most sought-after targets in lung cancer: KRAS G12C. KRAS G12C mutations occur in approximately 13% of lung adenocarcinomas and, after decades of being "undruggable," saw two drugs approved in 2021-2022 (sotorasib and adagrasib).
However, those first-generation KRAS G12C inhibitors only bind the inactive form of the KRAS protein ("OFF" state), and tumors often evolve resistance by keeping KRAS in an active GTP-bound state or through new mutations. BBOT's compound BBO-8520 is a "dual-state" covalent inhibitor of KRAS G12C; it can latch onto the mutant cysteine in both the ON (active) and OFF states of KRAS.
This means it could shut down KRAS G12C more completely and potentially remain effective even as the cancer tries to adapt. In late 2023, the FDA granted Fast Track Designation to BBO-8520 for previously treated KRAS G12C-mutant NSCLC, reflecting the need for better options after sotorasib/adagrasib failure.
BBO-8520 entered a Phase 1 trial (the FORT-2 study) in advanced solid tumors, and early results are anticipated in 2025. Preclinical data published in Cancer Discovery showed that BBO-8520 achieves "rapid and complete inhibition" of KRAS G12C-driven signaling by binding to KRAS's Switch II pocket and locking the protein in an inactive conformation.
Unlike first-gen agents, BBO-8520 doesn't require KRAS to cycle to OFF to bind; it can hit the active form, which is a first-in-class capability. In xenograft models, this led to deeper tumor regressions. The hope is that in patients, BBO-8520 will produce higher response rates or more durable responses, and could even work for those who progressed on sotorasib.
BBOT's financial backing comes from BridgeBio's ecosystem. Notably, BridgeBio's foundation in RAS science (through its affiliate Navire and partnerships with academia) helped identify this molecule. The oncology spin-out model means BBOT may have had dedicated $200+ million funding to push its RAS portfolio.
Looking ahead, BBOT's upcoming milestones include completing dose-escalation in Phase 1, reporting safety and any early efficacy signals. A Fast Track status will facilitate more frequent FDA interaction, potentially enabling an expedited path if results are striking in refractory patients.
BBO-8520's competitive differentiation is clear: if successful, it would be the next-generation KRAS G12C inhibitor that addresses resistance head-on. In an indication as competitive as KRAS, BBOT is effectively trying to outsmart both the cancer and its competitors by "drugging KRAS harder and smarter."
For lung cancer patients with KRAS G12C, especially those whose tumors no longer respond to existing drugs, this could mean a second chance at targeted therapy, an important development given the limited efficacy of salvage chemotherapy in that setting.
Technology: Targeted therapy (ROS1 inhibitor, next-gen, CNS-penetrant)
Lead Candidate: Taletrectinib (planned U.S. brand name pending approval)
Recent News: NDA accepted by FDA with Priority Review; PDUFA target date June 23, 2025 for taletrectinib in advanced ROS1+ NSCLC; China approved taletrectinib in Jan 2025; Phase 2 pivotal studies (TRUST-I/II) showed robust efficacy across patient subgroups
Nuvation Bio, a clinical-stage oncology company founded by industry veteran Dr. David Hung, has in-licensed and is advancing taletrectinib, a "next-generation" TKI for ROS1 fusion-positive NSCLC. ROS1 fusions, like ALK, are targetable drivers in a few percent of lung cancers. Crizotinib and entrectinib are approved ROS1 inhibitors, but their efficacy is limited by poor brain penetration and the emergence of resistance mutations (like ROS1 G2032R).
Taletrectinib was designed to overcome these issues: it's a potent ROS1/TRK inhibitor that crosses the blood-brain barrier and retains activity against known ROS1 mutations that confer resistance to crizotinib. Taletrectinib's clinical data have been impressive. Two pivotal single-arm Phase 2 trials, TRUST-I in China and TRUST-II globally, evaluated it in ROS1+ NSCLC both in TKI-naïve patients and those previously treated with crizotinib.
Combined results showed taletrectinib achieved high response rates with durable responses in both Asian and Western populations. Notably, it has shown efficacy in crizotinib-resistant patients, including those with the G2032R solvent-front mutation (a notorious resistance mechanism).
In January 2025, China's NMPA approved taletrectinib for adult patients with advanced ROS1-positive NSCLC, marking a major validation. In the U.S., Nuvation's NDA (filed in late 2024) was accepted and granted Priority Review with a PDUFA date of June 23, 2025.
The FDA also granted taletrectinib Breakthrough Therapy Designation for ROS1+ NSCLC regardless of prior TKI treatment, and Orphan Drug status. What sets taletrectinib apart is its broad efficacy: it appears effective in both ROS1 inhibitor-naïve patients (potentially positioning it as a new first-line standard) and in those who have failed prior ROS1 TKIs (where no targeted option existed).
Furthermore, patients with brain metastases responded to taletrectinib, underscoring its CNS activity, a crucial advantage since ROS1 lung cancer often metastasizes to the brain. Nuvation Bio secured rights to taletrectinib in 2022, pivoting from its internal programs to this high-impact opportunity.
Financially, Nuvation had a substantial war chest from its SPAC merger (over $800 million raised) and has indicated it can fund operations through key milestones. The company's stockpile enabled it to invest in commercial preparations in anticipation of a 2025 launch. Meanwhile, Nuvation continues its own NUV-868 (ATR inhibitor) and other programs, but taletrectinib is clearly the crown jewel now.
If approved in the U.S. and other Western markets, taletrectinib will intensify competition in ROS1+ NSCLC, likely becoming the best-in-class ROS1 inhibitor based on efficacy and brain penetration. Its development also highlights East-West collaboration: originally discovered in Asia (AnHeart Therapeutics), now being brought globally by Nuvation.
For patients, taletrectinib could mean longer disease control and better quality of life (due to delays in CNS progression) compared to the first-gen drugs. Given the priority review, the lung cancer community is eagerly awaiting mid-2025, as taletrectinib could soon offer a "truly meaningful new option" for ROS1-driven lung cancer, in the words of Nuvation's CEO.
Technology: Targeted therapy (RAS(ON) inhibitors that target active-state RAS mutations including KRAS G12C, G12D, etc.)
Lead Programs: RMC-6291 (RAS G12C(ON) inhibitor), RMC-6236 (pan-RAS multi inhibitor), RMC-9805 (RAS G12D inhibitor)
Recent News: Initial Phase 1 data for RMC-6291 showed tumor responses in KRAS G12C NSCLC even after prior KRAS inhibitor; RMC-6236 advancing in Phase 1 with activity across multiple KRAS mutations; presented first-in-human data for RAS G12D inhibitor (RMC-9865, aka "zoldonrasib") in 2024
Revolution Medicines (RevMed), based in California, is at the forefront of RAS-targeted therapy, a field of enormous importance since RAS mutations drive approximately 30% of cancers, including many lung adenocarcinomas. RevMed's approach is unique: they are developing RAS(ON) inhibitors, which bind to RAS in its active, GTP-bound state.
Traditional KRAS G12C drugs only bind the inactive GDP-bound form, but RAS(ON) inhibitors could attack mutants like KRAS G12C, G12D, G12V while they are "ON" and signaling, potentially yielding more potent and broader inhibition.
Their leading candidate RMC-6291 targets KRAS G12C in the active state. In late 2023, Revolution presented encouraging first-in-human data: in a Phase 1 trial, KRAS G12C-mutant NSCLC patients, including some previously treated with sotorasib or adagrasib, showed tumor regressions on RMC-6291.
The drug was tolerated across dose levels and demonstrated evidence of deeper target engagement (it caused near-complete shutdown of ERK phosphorylation in tumors for approximately 24 hours after a dose, per biopsy analyses). These early results hint that RMC-6291 might overcome some resistance mechanisms to first-gen KRAS inhibitors; for example, by binding KRAS in any conformation, it could inhibit cancer cells that adapt by keeping KRAS in an active state.
Revolution is now dose-escalating and combining RMC-6291 with their other RAS drug to see if further synergy is possible. Another key program is RMC-6236, a "RAS multi-selective" inhibitor designed to target multiple common RAS mutations (such as KRAS G12D, G12V, and N/HRAS variants) with one molecule.
This drug could benefit patients (including some NSCLC cases) who have RAS mutations other than G12C; for instance, KRAS G12D is prevalent in pancreatic cancer and present in a smaller subset of lung cancers. RMC-6236 is in Phase 1, and initial signals of efficacy in KRAS-mutant gastrointestinal and lung cancers have been observed, though details are pending publication.
Furthermore, Revolution has RMC-9805 (now known as zoldonrasib) specifically targeting KRAS G12D(ON). In early 2024 at AACR, they reported the first ever clinical data of a KRAS G12D inhibitor: in a few evaluable patients with KRAS G12D tumors (including pancreatic and possibly lung), partial responses were seen, demonstrating "encouraging initial antitumor activity."
This is a landmark, as KRAS G12D had been considered undruggable until now. On the financial side, Revolution Medicines has a strong balance sheet, helped by a $650 million partnership with Sanofi (for a SHP2 inhibitor program) and a follow-on equity raise in 2023 when enthusiasm for RAS was high. They have cash to fund their multiple trials through important milestones.
One noteworthy strategic move: RevMed is exploring combination therapy within its RAS franchise; e.g., combining a KRAS G12C(ON) inhibitor with the RAS multi-inhibitor to shut down heterogeneous mutant RAS populations, an approach already being tested in clinic. If successful, this could delay or prevent resistance.
Revolution's competitive differentiation is its deep scientific focus on RAS biology and a pipeline covering various mutant forms. It is essentially building a "RAS toolkit" for oncologists. In lung cancer, where KRAS mutations (esp. G12C) are common, Revolution could provide a second-generation solution for G12C cases who fail first-gen drugs, and the first targeted therapies ever for KRAS G12D or KRAS G12V cases that currently have none.
This breadth is unmatched by any competitor. If their drugs live up to the name, they truly will be revolutionary, potentially enabling combination therapies that tackle the adaptability of RAS-driven cancers head-on, and significantly improving outcomes for patients with RAS-mutant lung cancers.
Technology: Immunotherapy (soluble LAG-3 protein to activate antigen-presenting cells)
Lead Candidate: Eftilagimod alpha (IMP321, "efti")
Recent News: Phase 2 data (INSIGHT-003) showed efti + pembrolizumab + chemo achieved 32.9 months median OS in first-line NSCLC, vastly exceeding historical 22 months; completing enrollment for Phase 2 in PD-1 resistant NSCLC; planning Phase 3 with a partner
Immutep, a biotech from Australia (with operations in Europe), is developing a novel immunotherapy that doesn't directly target T-cells like PD-1 or CTLA-4, but instead boosts the upstream immune response. Its lead, eftilagimod alpha (efti), is a soluble fusion protein of LAG-3.
Unlike anti-LAG-3 antibodies that block LAG-3 on T-cells, efti leverages LAG-3's natural function as an immune booster: it binds to MHC II molecules on dendritic cells (antigen-presenting cells), acting as a "MHC II agonist". The result is increased activation of dendritic cells and monocytes, leading to better priming of anti-tumor T-cells. In essence, efti functions as an immune adjuvant, turning "cold" tumors "hot" or enhancing the effect of other immunotherapies.
Immutep has been combining efti with pembrolizumab (Keytruda) in trials, similar to how biotech companies are exploring innovative combination approaches in drug discovery, hypothesizing that efti can drive more antigen presentation and T-cell generation, which PD-1 therapy then unleashes. Results have been eye-catching.
In the Phase 2 INSIGHT-003 study, efti + pembrolizumab + chemotherapy was given first-line to 1L NSCLC patients (regardless of PD-L1 status). The regimen delivered an overall response rate of approximately 55% and, notably, seemed to benefit even traditionally non-immunogenic tumors; patients with PD-L1-negative tumors had a 47
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