On April 7, 2024 Dizal (688192.SH) reported that the U.S. Food and Drug Administration ("FDA") has granted Breakthrough Therapy Designation (BTD) to its sunvozertinib as the first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations (Press release, Dizal Pharma, APR 7, 2024, View Source;patients-with-advanced-non-small-cell-lung-cancer-harboring-egfr-exon-20-insertion-mutations-302109862.html [SID1234641847]).

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This Breakthrough Therapy Designation (BTD) approval was based on results from the global multi-center phase I/II study (WU-KONG1). At 2023 ESMO (Free ESMO Whitepaper), Dizal reported main study results, showing sunvozertinib as a single agent with confirmed objective response rate (cORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months.

Sunvozertinib was previously granted BTDs by both the US FDA and the China Center for Drug Evaluation (CDE) for relapsed or refractory patients It was subsequently approved in China in 2023 for the treatment of patients who failed 1st line treatment. NDA submissions for US and EU approvals in the same setting is anticipated later in 2024.

"We are delighted with the FDA’s decision granting the Breakthrough Therapy Designation to sunvozertinib for first-line treatment, coming on the heels of earlier BTD approval in later lines of therapy — a clear indication of sunvozertinib’s transformative potential in the treatment of patients with EGFR exon20ins NSCLC. Multiple clinical trials have consistently demonstrated sunvozertinib’s significant clinical benefits to our patients. As a single, oral agent, it offers apparent advantages in both safety and patient compliance over chemotherapies and infusion." said Xiaolin Zhang, PhD, CEO of Dizal, "Now enrollment for the global pivotal study in relapsed and refractory setting (WU-KONG1 PART B) has been completed, and we are going to report the study results as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. A randomized global phase III study in the first line setting (WU-KONG28) is well underway. This new BTD will enable us work more closely with the FDA and accelerate its clinical development and regulatory submission."

Affecting roughly 2%-4% of NSCLC patients, EGFR Exon20ins mutations have been difficult to treat due to their unique spatial conformation, diverse mutation subtypes, and high heterogeneity. There has been a persistent lack of safe and effective targeted treatment options for this mutation, leading to limited survival benefits for patients.

Sunvozertinib’s innovative molecular structure enables it to overcome the inherent difficulties of targeting EGFR Exon20ins mutations, offering improved efficacy, safety, and ease of administration. Supported by findings yielded in the multicenter phase 2 pivotal study WU-KONG6, sunvozertinib was approved in China for the treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations whose disease has progressed on or following platinum-based chemotherapy, validating its potent and well-tolerated profile in previously treated NSCLC patients with EGFR Exon20ins mutations.

About Breakthrough Therapy Designation

The FDA’s Breakthrough Therapy Designation is intended to expedite the development and regulatory review of drugs for serious or life-threatening conditions. To qualify, new drugs must demonstrate promising preliminary clinical results indicating substantial improvement on clinically significant endpoints over existing treatments. Drugs designated as breakthrough therapies benefit from a suite of accelerated development policies, including close guidance by FDA experts throughout the clinical development process, significantly improving communication efficiency. Upon submission of a marketing application, such drugs may also be eligible for priority review if they meet relevant criteria.

About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA for the treatment of advanced NSCLC with EGFR exon20ins mutations after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins mutations. The primary endpoint of the study, which was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. Anti-tumor efficacy was observed across a broad range of EGFR exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins mutations.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug related TEAEs (treatment emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 PART B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR Exon20ins mutations.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery (IF:39.397) and The Lancet Respiratory Medicine (IF: 76.2).

On April 7, 2024 Geneos Therapeutics, a clinical stage biotherapeutics company focused on the development of personalized therapeutic cancer vaccines (PTCVs), reported the publication of positive safety, immunogenicity, and efficacy data from the full cohort of patients enrolled in its GT-30 clinical trial in Nature Medicine (Press release, Geneos Therapeutics, APR 7, 2024, View Source [SID1234641846]).

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The paper, titled, "Personalized Neoantigen Vaccine and Pembrolizumab in Advanced Hepatocellular Carcinoma: A phase 1/2 trial," details the GT-30 clinical trial, a 36-patient, single-arm, open-label, multi-center Phase 1/2 study of GNOS-PV02, a DNA plasmid encoded PTCV in combination with DNA plasmid encoded IL-12 (a cytokine adjuvant), and pembrolizumab (a PD-1 inhibitor) in second-line (2L) patients with advanced hepatocellular carcinoma (HCC) previously treated with a multi-tyrosine kinase inhibitor. The study met its primary endpoints of safety and immunogenicity and its secondary endpoint of efficacy based on observed response rate (ORR).

PTCV-related adverse events were all limited to Grades 1 and 2 with no dose-limiting toxicities or grade > 3 adverse events observed. The most common adverse events were injection site reactions observed in 41.6% (15/36) of patients. This is in contrast to typical immuno-oncology combination regimens, including those approved for first-line use in advanced HCC, wherein adding a second agent may lead to markedly increased toxicity; here, the addition of a PTCV to a PD-1 inhibitor was not observed to lead to any significant decrease in patient safety and tolerability.

The ORR for GT-30 is currently at 30.6% (11/36), including three complete responses (CR) and eight partial responses. This response is statistically significant based on pre-specified criteria at a one-sided p-value = 0.031 (1-sided 90% CI 20.4%-100%) versus a pre-specified historical control of 16.9% for pembrolizumab monotherapy. This historical comparator response rate was modeled on Phase 3 KN-240 data presented at ASCO (Free ASCO Whitepaper) 2019 and is also consistent with the prior Phase 2 KN-224 study. As an overall class, anti-PD1 monotherapy for 2L advanced HCC has shown response rates of 11%-18% in seven Phase 2 and Phase 3 clinical studies enrolling over 1400 patients. Additionally, the GT-30 CR rate of 8.3% (3/36) compares with a historical anti-PD-1 monotherapy CR rate in 2L of 0% – 3% in the prior studies. As of the data cutoff, the median OS (mOS) in GT-30 was 19.9 months compared to a mOS range of 12.9 – 15.1 months reported for the prior 2L studies of pembrolizumab and other anti-PD-1 monotherapy. 11 of 36 patients remain on treatment and, in total, 17 patients continue to be followed for overall survival (OS).

"Other recent industry trials have tested personalized cancer vaccines in patients with highly immune-sensitive tumor phenotypes and no measurable disease. In marked contrast, the GT-30 trial assesses PTCVs in HCC, a cancer with very low tumor mutational burden and an immune-excluded phenotype, and in patients with significant late-stage unresectable and metastatic disease," said Niranjan Sardesai, PhD, CEO and president of Geneos. "Despite the small size of this study, our results are important for the advancement of the field. We have not only met endpoints for safety, immunogenicity, and clinical efficacy based on ORR in this difficult to treat setting, but our mechanism of action data trace and confirm every step, from vaccination to tumor reduction, required to explain the immunological basis for the observed clinical responses."

Immunological analyses confirm the induction of new T cell responses to vaccine-encoded neoantigens in 14 of 14 (100%) evaluated patients and the expansion of this TCR repertoire both in the peripheral blood and tumors of PTCV-treated patients. Single cell sequencing analyses show the vast majority of these T cell clones to be CD8 T effector memory cells, a key requirement to induce anti-tumor cytotoxicity. In contrast, while anti-PD-1 monotherapy has been observed to reverse T cell dysfunction in existing neoantigen-specific T cell clones, it is not known to induce any new neoantigen-specific T cell clones.

Today Geneos also presented selected GT-30 clinical trial data and updated longitudinal circulating tumor DNA (ctDNA) biomarker data from the trial at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego. Reductions of at least 50% versus baseline in patient ctDNA, an exploratory endpoint, were seen in 40.7% of patients (11 of 27 patients for whom the full data set are available). All such responses correlate with ongoing survival.

"To our knowledge, the GT-30 clinical study provides the first definitive demonstration of a personalized cancer vaccine enhancing clinical response to anti-PD-1 therapy by inducing new, neoantigen-specific T cells which traffic to the tumor," said Ildiko Csiki, MD, PhD, chief medical officer of Geneos. "The fact that the PTCV regimen has produced this important result in a form of cancer as immunologically ‘cold’ as HCC, leading to multiple complete responses and a doubling of objective response versus PD-1, is incredibly promising and shows the therapeutic potential of personalized cancer vaccines for cancer patients."

DNA-based PTCVs may include up to 40 neoantigens. The majority of patients in the GT-30 study were administered PTCVs which included all of their targetable neoantigens across a broad range of predicted MHC binding affinity. A correlation was seen in GT-30 between the number of vaccine epitopes and the number of reactive epitopes post-vaccination, suggesting that having more neoantigens in the vaccine increased the effectiveness of tumor control. Other personalized vaccine platforms, especially those not based on DNA, have historically had to target a more limited selection of neoantigens, which may limit their efficacy.

On April 7, 2024 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 are presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (Press release, Innovent Biologics, APR 7, 2024, View Source [SID1234641845]).

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Late-Breaking Research: Experimental and Molecular Therapeutics 1

Topic: IBI3001: a potentially first-in-class site-specific glycan-conjugated B7-H3/EGFR bispecific ADC for multiple solid tumors
Abstract Number: LB055
Presentation Form: Poster
Presentation Time: Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

IBI3001 is a potentially first-in-class bispecific ADC against B7-H3 and EGFR that is site-specifically glycan-conjugated using the clinically validated SYNtecanE platform.

IBI3001 has multiple anti-tumor mechanisms of action: (1) enhanced EGFR signaling blockade; (2) EGFR- and B7-H3-aided payload internalization and cytotoxicity; and (3) potent bystander killing effects of ADC. The optimized B7-H3 arm not only enhances the EGFR signaling blockade but also reduces EGFR on-target toxicities.

IBI3001 showed strong anti-tumor efficacy in vitro and in vivo across multiple solid tumors and is well tolerated with the therapeutic index at 40.

Topic: IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, demonstrated potent pre-clinical efficacy in solid tumors
Abstract Number: LB056
Presentation Form: Poster
Presentation Time: Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

IBI334 is an afucosylated bispecific antibody against B7-H3 and EGFR that is constructed using Innovent’s proprietary Innobody platform.

With the aid of B7-H3, IBI334 showed better tumor growth inhibition in vitro and in vivo than EGFR monoclonal antibody and c-met/EGFR bispecific antibody benchmarks.

IBI334 has a favorable safety profile with the highest non-severely toxic dose (HNSTD) in cynomolgus monkeys at 120 mg/kg and a large therapeutic window of > 200 folds.

As a promising bispecific antibody against multiple solid tumors, IBI334 is currently under clinical evaluation.

Topic: Discovery and preclinical characterization of IBI343, a site-specific glycan-conjugated anti-Claudin18.2 ADC for treating solid tumors
Abstract Number: LB057
Presentation Form: Poster
Presentation Time: Sunday Apr 7, 2024 1:30 PM – 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He

IBI343 is a potentially first-in-class anti-Claudin 18.2 ADC that is site-specifically glycan-conjugated to cytotoxin exatecan via Synaffix’s GlycoConnect technology.

It demonstrated Claudin 18.2-specific in vitro cytotoxicity on a series of cancer cell lines at varying levels of target expression, and potent in vivo efficacy in multiple xenograft models. The glycan-based conjugation technology leads to enhanced stability of the ADC molecule. IBI343 displayed good safety profile in GLP toxicology study in rhesus monkey and was well tolerated up to 30 mg/kg.

IBI343 has favorable pre-clinical efficacy and safety, and it is currently in preparation for Phase 3 clinical trial for Claudin-18.2-positive HER2-negative gastric cancer.

Dr. Kaijie He, Vice President of Innovent, stated: "We are pleased that the pre-clinical studies of our novel anti-cancer drugs are accepted for Late-Breaking Research poster presentation at the 2024 AACR (Free AACR Whitepaper) conference. This is the result of dedicated work from scientists at Innovent Academy with the aim to tackle cancers with innovative drugs that are more effective and safer. With careful design and optimization, our molecules can achieve favorable therapeutic windows of 40 to more than 200 times. We look forward to their performance in clinical settings and hope that these innovations can eventually benefit cancer patients."

Poster Session: Immunology – Single Target and Bispecific Antibodies

Topic: A novel TROP2-targeted immune stimulating antibody conjugate (ISAC) with potent anti-tumoral activity and acceptable safety
Abstract Number: 2718
Presentation Form: Poster
Presentation Time: Monday Apr 8, 2024 1:30 PM – 5:00 PM
Location: Poster Section 6
Poster Board Number: 9
Presenting Author: Dr. Huizhong Xiong

Immune stimulating antibody conjugates (ISACs) are a unique class of ADC in which antibodies recognizing tumor antigens are conjugated with immune agonists. ISACs target tumor tissue and specifically activate intra-tumoral myeloid cells, unleashing downstream immune response. Like the other immune agonists, balance between efficacy and safety remains a challenge for ISACs.

Here we describe a potential first-in-class TROP2 ISAC with rationally selected antibody and TLR7/8 agonist linker-payload. The anti-TROP2 antibody elicited robust ADCP of TROP2+ tumor cells by macrophages. In-vitro, TROP2 ISAC mildly activated myeloid cells only in the presence of TROP2+ tumor cells. In-vivo, the molecule potently suppressed tumor growth in different TROP2+ xenograft tumors, and effectively enhanced killing of an ADC. In terms of safety, the ISAC was tolerated in both WT and hTROP2KI mice, and, importantly, in monkeys.

Taken together, our data demonstrate a novel TROP2 ISAC with outstanding efficacy and manageable safety profile, which may benefit patients with TROP2+ tumors.

Poster Session: Immunology – Immune Modulation Employing Agonist or Co-Stimulatory Approaches

Topic: Tumor targeted-CD28 bispecific antibody with optimized potency, robust anti-tumoral activity and stringent CD3-dependence
Abstract Number: 5295
Presentation Form: Poster
Presentation Time: Tuesday Apr 9, 2024 1:30 PM – 5:00 PM
Location: Poster Section 3
Poster Board Number: 4
Presenting Author: Dr. Huizhong Xiong

We reported a rationally screened CD28 agonist antibody and its PSMAxCD28 bispecific format, IAR038.

IAR038 has minimal activity in the absence of CD3, even under stringent conditions, different from benchmark antibody in clinical development. It demonstrated moderate activity in vitro in a CD3-dependent and PSMA-dependent manner. Notably, IAR038 elicited superior tumor killing in vivo and combined effectively with anti-PD1 antibody.

In addition, it had an improved half-life compared with the Benchmark antibody. These features may translate to a wider therapeutic window and improved safety for CRPC patients.

Dr. Huizhong Xiong, Senior Director of Immunology of Innovent, stated: "We keep pushing for deeper understanding and more rational design of agonistic and costimulatory molecules. Our work on tumor targeted TLR7/8 agonist and tumor targeted CD28 antibody demonstrates the capability of our biology-driven drug development to achieve better balance between efficacy and safety, made possible by our advanced technology platforms."

On April 7, 2024 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, reported a poster presentation of preclinical data on EOS-984, a potential first-in-class small molecule inhibitor targeting the equilibrative nucleoside transporter 1 (ENT1) in oncology, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 5-10, 2024 in San Diego, California (Press release, iTeos Therapeutics, APR 7, 2024, View Source [SID1234641843]).

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Based on the Company’s discovery and characterization of ENT1 in adenosine-mediated immunosuppression, this novel mechanism allows for the intracellular accumulation of adenosine, which then suppresses proliferation and effector function of T cells in the high adenosine tumor microenvironment. In mouse models, deletion of ENT1 led to potent control of tumor proliferation and increased CD8+ T cell frequency, proliferation, and cytokine production within tumors, further supporting ENT1’s role in tumor growth. In preclinical studies, blockade of intracellular adenosine accumulation by EOS-984 enabled proliferation of memory T cells and TILs despite high adenosine concentrations, resulting in the restoration of T cell function and enhanced tumor cell killing. Furthermore, combination of EOS-984 with anti-PD-1 therapy synergistically led to the control of tumor growth in a humanized mouse model of triple negative breast cancer resistant to anti-PD-1 blockade. Due to its mechanism of action, EOS-984 holds potential as a combination partner beyond anti-PD-1 therapy, including other immuno-oncology agents, cell therapies, and bispecific T cell engagers.

EOS-984 is currently in the dose escalation portion of a Phase 1 trial in advanced malignancies. Topline data from the Phase 1 trial is anticipated in the second half of 2024.

Abstracts are available on AACR (Free AACR Whitepaper)’s website located at www.aacr.org. Posters will be archived in the Investors section of the Company’s website located at www.iteostherapeutics.com.

Poster Presentation Details

Title: "Inhibition of equilibrative nucleoside transporter 1 relieves intracellular adenosine-mediated immune suppression"
Session Title: Experimental and Molecular Therapeutics: Tumor Microenvironment
Abstract Number: 734
Date and Time: Sunday, April 7, 2024, 1:30 p.m. – 5:00 p.m. PT
Location: Poster Section 29

About iTeos Therapeutics, Inc.

iTeos Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients. iTeos Therapeutics leverages its deep understanding of tumor immunology and immunosuppressive pathways to design novel product candidates with the potential to restore the immune response against cancer. The Company’s innovative pipeline includes three clinical-stage programs targeting novel, validated immunosuppressive pathways designed with optimized pharmacologic properties for improved clinical outcomes, including the TIGIT/CD226 axis and the adenosine pathway. iTeos Therapeutics is headquartered in Watertown, MA with a research center in Gosselies, Belgium.

About EOS-984

EOS-984 is a potential first-in-class small molecule targeting the equilibrative nucleoside transporter 1 (ENT1) designed to inhibit the immunosuppressive activity of adenosine and restore immune cell proliferation. The therapeutic candidate has the potential to fully reverse the profound immunosuppressive action of adenosine on T and B cells and is in Phase 1 development.

On April 7, 2024 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported real-world evidence of the evolving epidermal growth factor receptor (EGFR) mutation landscape in non-small cell lung cancer (NSCLC), and the potential of BDTX-1535 to address a broader range of mutations compared to existing therapies (Press release, Black Diamond Therapeutics, APR 7, 2024, View Source [SID1234641842]). The results were disclosed in an oral presentation on April 7, 2024, at the 2024 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held in San Diego, California.

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The oral presentation, titled "BDTX-1535 – A MasterKey EGFR Inhibitor Targeting Classical, Non-Classical and the C797S Resistance Mutation to Address the Evolved Landscape of EGFR Mutant NSCLC," evaluated more than 235,000 sequenced cases of NSCLC sourced from Guardant Health (GuardantINFORM) and Foundation Medicine (FoundationInsights). The analyses reveal a broad spectrum of non-classical mutations, as well as an increased prevalence of the acquired resistance mutation, C797S. Over 100 unique non-classical EGFR oncogenic driver mutations were identified in newly diagnosed patients with NSCLC, and these non-classical EGFR mutations were present in 20-30% of patients across all lines of treatment.

"The landscape of EGFR mutations in NSCLC continues to evolve, revealing classical and non-classical driver mutations," said John Heymach, M.D., Ph.D., Chair of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center. "Non-classical mutations fall into categories including kinase domain PACC mutations and ectodomain mutations; therefore, next generation EGFR targeted therapies must effectively cover multiple subgroups of mutations."

"Novel targeted therapies are still needed to continue to improve clinical outcomes for patients with EGFR-mutant lung cancers," added Xiuning Le, M.D., Ph.D., Associate Professor, Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center. "To extend survival for our patients, newer drugs need to have good mutational coverage, good tolerability, and good brain penetrance."

Preclinical data demonstrated that BDTX-1535 potently inhibits more than 50 clinically relevant, non-classical EGFR mutations (as well as the classical L858R and exon19-del mutations) while sparing wild-type EGFR. The compound also potently inhibits the drug resistance C797S mutation, which emerges following treatment with third-generation EGFR inhibitors, including osimertinib. Real-world data indicate non-classical EGFR mutations can be co-expressed with classical mutation L858R, a setting that has been characterized by shorter duration of response to osimertinib first-line therapy. Preclinical data show that BDTX-1535 potently inhibits these co-expressed non-classical mutations.

"BDTX-1535 was designed to address a broad spectrum of more than 50 non-classical oncogenic EGFR mutations, as well as the C797S resistance mutation," said Elizabeth Buck, Ph.D., Chief Scientific Officer and co-founder of Black Diamond Therapeutics. "We believe that the potency of BDTX-1535 against the full spectrum of classical, non-classical, and C797S mutations positions the compound as the first and best-in-class fourth-generation EGFR inhibitor potentially offering NSCLC patients a well-tolerated, brain-penetrant, oral therapy across various lines of treatment."

Phase 1 proof-of-concept data demonstrating durable responses in recurrent NSCLC patients with both non-classical and acquired resistance C797S mutations were presented in October 2023. Black Diamond is currently advancing BDTX-1535 in a Phase 2 trial for patients with EGFRm NSCLC across multiple lines of therapy. Patients are being enrolled both in a first-line (1L) setting (for those expressing EGFR non-classical mutations) and in second- and third-line (2L/3L) settings following prior treatment with an EGFR inhibitor. Initial results from 2L/3L patients are anticipated in the third quarter of 2024.

About BDTX-1535
BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC), including classical driver mutations, non-classical driver mutations, and the acquired resistance C797S mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A "window of opportunity" trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290).