On September 3, 2025 enGene Holdings Inc. (Nasdaq: ENGN, "enGene" or the "Company"), a clinical-stage, non-viral gene therapy company, reported it has achieved its target enrollment milestone of 100 patients for the pivotal cohort of its ongoing, open-label, multi-cohort Phase 2 LEGEND trial of detalimogene voraplasmid ("detalimogene" and previously EG-70) in patients with high-risk, non-muscle invasive bladder cancer (NMIBC) (Press release, enGene, SEP 3, 2025, View Source [SID1234655749]). LEGEND’s pivotal Cohort 1 is studying detalimogene in patients with high-risk NMIBC with carcinoma in-situ (CIS) with or without concomitant papillary disease. Patients in the screening process remain eligible for potential enrollment in the trial. The Company expects to overenroll in its pivotal cohort resulting in an adjustment in guidance for a BLA submission to 2H 2026.

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"Achieving our target enrollment goal for detalimogene in LEGEND’s pivotal cohort represents an important milestone for enGene. It brings us a step closer to our goal of providing patients and physicians with the first non-viral gene therapy that offers a unique balance of efficacy, safety, and ease-of-use," said Ron Cooper, Chief Executive Officer of enGene. "We are grateful to study participants, investigators, and our clinical organization for their contributions to advancing the development of detalimogene."

About Detalimogene Voraplasmid

Detalimogene is a novel, investigational, non-viral gene therapy for patients with high-risk, non-muscle invasive bladder cancer (NMIBC), including Bacillus Calmette-Guérin (BCG)-unresponsive disease. It is designed to be instilled in the bladder and elicit a powerful yet localized anti-tumor immune response.

Detalimogene was developed using the Company’s Dually Derivatized Oligochitosan (DDX) platform, a technology designed to transform how gene therapies are accessed by patients and utilized by clinicians. Medicines developed with the DDX platform can potentially overcome the limitations of viral-based gene therapies, reduce complexities related to safe handling and cold storage, and streamline both manufacturing processes and administration paradigms.

Detalimogene has received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the U.S. Food and Drug Administration (FDA) based on its potential to address the high unmet medical need for patients with BCG-unresponsive carcinoma in situ (CIS) NMIBC with or without resected papillary tumors who are unable to undergo cystectomy. The RMAT program is intended to expedite the development and review of regenerative medicine therapies for serious or life-threatening conditions, where preliminary clinical evidence suggests potential to address unmet medical needs. Similarly, Fast Track designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

About the LEGEND Trial

Detalimogene is being evaluated in the ongoing, open-label, multi-cohort, Phase 2 LEGEND trial to establish its safety and efficacy in high-risk NMIBC. LEGEND’s pivotal cohort (Cohort 1) consists of approximately 100 patients with high-risk, BCG-unresponsive NMIBC with CIS (with or without papillary disease) and is designed to serve as the basis of the Company’s planned Biologics License Application (BLA) filing. In addition to this pivotal cohort, LEGEND includes three additional cohorts, including NMIBC patients with CIS who are naïve to treatment with BCG (Cohort 2a); NMIBC patients with CIS who have been exposed to BCG but have not received adequate BCG treatment (Cohort 2b); and BCG-unresponsive high-risk NMIBC patients with papillary-only disease (Cohort 3). The LEGEND trial is actively enrolling patients with sites participating in the USA, Canada, Europe, and the Asia-Pacific region.

On September 3, 2025 Treeline Biosciences (or Treeline) reported the initiation of Phase 1 trials for two internally discovered programs, TLN-121 and TLN-372, and a third in-licensed program, TLN-254 (Press release, Treeline Biosciences, SEP 3, 2025, View Source [SID1234655748]). TLN-121, a BCL6 degrader, and TLN-254, an EZH2 inhibitor, are both being studied in patients with lymphoma. TLN-372, a pan-KRAS inhibitor, is being studied in patients with cancers expressing certain KRAS mutations. The company also announced the close of a $200 million Series A extension, bringing total funding to $1.1 billion.

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"We aspire to create the next great enduring biopharma company," said Josh Bilenker, M.D., Treeline’s Co-Founder and CEO. "Our funding mandate has allowed us to recruit proven scientists, rigorously test assumptions and curate a pipeline from parallel discovery efforts. BCL6 and KRAS are formidable targets that required difficult chemistry and novel assay development. We hope these programs deliver for patients and create momentum for our next set of clinical entries."

Go here to read more of Josh’s perspective on today’s news.

Treeline Facts

Co-founded by CEO Josh Bilenker and CSO Jeff Engelman, both oncologists with experience leading R&D teams. Josh previously founded Loxo Oncology, which developed three FDA-approved medicines. Jeff was director of thoracic oncology at Massachusetts General Hospital and later global head of oncology at the Novartis Institutes for BioMedical Research.
Internal R&D team uses leading-edge computational tools to prioritize workflow and accelerate timelines.
Therapeutic areas include cancer, neurological and autoimmune diseases.
Programs include small molecules, degraders and glues, and targeted therapy ADCs (TT-ADCs).
Team and pipeline were built for scaled invention and company longevity.
$1.1 billion raised to-date, including a recent $200M Series A extension; investors include: AI Life Sciences, an affiliate of Access Industries; ARCH Venture Partners; OrbiMed; GV; KKR; accounts advised by T. Rowe Price Associates, Inc.; Ajax Health/Zeus; Casdin Capital; Fidelity Management & Research Company; Aisling Capital; Rock Springs Capital; and Exor.
Medicines in the Making

Treeline’s founding team has worked extensively in cancer R&D, and its first three clinical programs reflect this hard-won experience:

TLN-121 — BCL6 Protein Degrader for Lymphomas
BCL6 is a naturally occurring protein that certain lymphoma cells exploit to silence genes that would otherwise block their growth and survival. TLN-121 is a protein degrader designed to remove BCL6 from cancer cells while avoiding off-target effects that could cause toxicity, potentially enabling combination use with standard-of-care lymphoma therapies. The Phase 1 trial (NCT07082803) is enrolling patients with B-cell and T-cell lymphomas.

TLN-372 — Pan-KRAS Inhibitor for Solid Tumors
Approximately one in four adult cancers harbor a KRAS alteration. While there are FDA-approved medicines for G12C mutations, other KRAS variants remain unaddressed by targeted therapies. TLN-372 is a small molecule inhibitor with novel chemistry designed for deep, continuous pan-KRAS inhibition, and possesses favorable drug-like properties. The Phase 1 trial will enroll patients with KRAS-altered solid tumors.

TLN-254 — EZH2 Inhibitor for Lymphomas
EZH2 regulates gene expression and is often overexpressed or mutated in cancers. TLN-254 is a small molecule inhibitor that was in-licensed after Phase 2 testing in refractory lymphoma. The Phase 1 trial (NCT06733441) is enrolling patients with peripheral and cutaneous T-cell lymphomas.

On September 3, 2025 Iambic Therapeutics, a clinical-stage life science and technology company developing novel medicines using its AI-driven discovery and development platform, reported it will present new pre-clinical NSCLC data for its lead drug candidate, IAM1363, at the IASLC 2025 World Conference on Lung Cancer (Press release, Iambic Therapeutics, SEP 3, 2025, View Source [SID1234655747]).

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IAM1363 is a potent, irreversible Type II HER2 inhibitor, highly differentiated by its target selectivity (>5,000-fold HER2 vs EGFR selectivity), brain-penetrance, pan-mutant activity, and tumor enrichment. New IAM1363 data show potent anti-tumor activity and significant tumor regression across a panel of HER2-amplified and HER2-mutant NSCLC models, including greater anti-tumor activity compared to currently approved therapies. Importantly, IAM1363 demonstrated robust anti-tumor activity with prolonged survival in an intracranial model of brain metastasis. Finally, treatment with IAM1363 resulted in striking tumor enrichment in a HER2 exon 20-mutant NSCLC model with strong tumor regression.

IAM1363 is currently advancing in an ongoing Phase 1/1b clinical trial.

Poster: IAM1363 Is a Potent, Selective, and Irreversible HER2 and Pan-HER2 Mutant Small Molecule Inhibitor for the Treatment of HER2-Driven NSCLC

Session and Presentation: Tumor Biology – Translational Biology, #P3.03.29

Presenter: John Huang, PhD, VP of Biology, Iambic Therapeutics

Time and Location: Tuesday, September 9, 2025, 10:00 AM CEST, Fira de Barcelona Convention Center, Exhibit Hall

On September 3, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported it will host a call to discuss the ivonescimab data from our global Phase III clinical trial, HARMONi, presented as part of the Presidential Symposium at the International Association for the Study of Lung Cancer’s (IASLC) 2025 World Conference on Lung Cancer (WCLC 2025) in Barcelona, Spain (Press release, Summit Therapeutics, SEP 3, 2025, View Source [SID1234655746]). The call will be held on Monday, September 8, 2025, at 8:00am ET and will be accessible through our website, www.smmttx.com. An archived edition of the session will be available on our website.

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HARMONi is a multiregional, double-blinded, placebo-controlled, Phase III study sponsored by Summit evaluating ivonescimab plus platinum-doublet chemotherapy compared to placebo plus platinum-doublet chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed after treatment with a 3rd generation EGFR tyrosine kinase inhibitor (TKI).

About Ivonescimab

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

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, SITC (Free SITC Whitepaper), 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 2,800 patients have been treated with ivonescimab in clinical studies globally.

Summit began its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. Additionally, in early 2025 the Company began enrolling patients in the United States for HARMONi-7.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib). Enrollment in HARMONi was completed in the second half of 2024, and top-line results were announced in May of 2025.

HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression.

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

In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.

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

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

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

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (FDA) for the HARMONi clinical trial setting.

On September 3, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company focused on innovative cancer therapeutics, reported participation and presentation of initial Phase 1 data of ENV105 in non-small cell lung cancer by Principal Investigator Dr. Karen Reckamp. Dr. Reckamp will present at the World Lung Cancer Conference which takes place September 6-9, 2025, at the Fira de Barcelona Gran Via in Barcelona, Spain (Press release, Kairos Pharma, SEP 3, 2025, View Source [SID1234655745]).

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Dr. Reckamp’s presentation, "Combination of Osimertinib and Carotuximab for Advanced, EFGR-Mutated Non-Small Cell Lung Cancer Patients," focuses on combination therapy of ENV105 with osimertinib for the treatment of non-small cell lung cancer. More information on the trial can be found here.

The primary objective of the open-label trial is to evaluate the safety and tolerability of the combination therapy.