On April 20, 2026 Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported updates from its EphA2 pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026.

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"EphA2 is a potentially high value target that is widely expressed in cancer and has been considered undruggable following the failure of multiple antibody-based approaches due to toxicity or insufficient efficacy. Encouraging results presented at AACR (Free AACR Whitepaper) demonstrate the potential of our Bicycle platform to drug this target with a generally well tolerated and differentiated safety profile and enhances our understanding of how best to deploy EphA2-targeted therapeutics," said Bicycle Therapeutics CEO Kevin Lee, Ph.D. "Nuzefatide pevedotin has demonstrated an emerging differentiated safety profile as a monotherapy and in combination with a checkpoint inhibitor, in over 150 patients to date. Consequently, using a combination of expression analysis, preclinical patient-derived xenograft efficacy studies, and human patient imaging, we have identified significant opportunities for this molecule in a number of cancers, including pancreatic cancer."

Dr. Lee added: "We have now identified 8mg/m2 Q2W as the preferred dose for monotherapy. Our strategy is to initially develop nuzefatide in pancreatic cancer where patients have limited available treatment options, and in parallel, to bring forward the next generation of EphA2-targeted radiotherapeutics to build on our foundational work in bladder and other EphA2-expressing tumors. Following this strategy, I am very pleased to announce that the first patient in our 2L+ pancreatic ductal adenocarcinoma Phase 2 study has been successfully dosed."

AACR Annual Meeting 2026 Data Highlights

Nuzefatide pevedotin (nuzefatide), formerly BT5528, a potentially first-in-class EphA2 targeting Bicycle Drug Conjugate (BDC), Phase 1/2 data in combination with nivolumab in metastatic urothelial cancer (mUC) patients. As of the February 9, 2026 data cutoff, results from the Phase 1/2 trial evaluating nuzefatide 6.5mg/m2 once every two weeks (Q2W) plus nivolumab 480mg once every four weeks (Q4W) in 14 patients with mUC who had previously progressed on a checkpoint inhibitor (10 while on enfortumab vedotin) showed:
40% confirmed overall response rate (ORR) (4/10) among patients with EphA2+ tumors and 100% confirmed ORR (3/3) among patients with EphA2+ tumors that were monomethyl auristatin E (MMAE)-naïve.
Patients who achieved a partial response (PR) or at least 16 weeks of stable disease (SD) were on treatment for a minimum of 56 weeks and most continued on treatment at the time of the data cut-off.
Nuzefatide in combination with nivolumab was generally well tolerated with no Grade ≥3 treatment-related adverse events (TRAEs) of clinical interest and no TRAEs of haemorrhage observed. Only one dose-limiting toxicity of Grade 3 fatigue that lasted for five days was reported and improved to Grade 1 without dose reduction.
In contrast to other EphA2-targeted agents, nuzefatide has demonstrated a positive emerging efficacy and safety profile in over 150 patients with hard-to-treat tumors to date. Further work has led Bicycle Therapeutics to determine 8mg/m2 Q2W as the preferred dose for the Phase 2 trial in patients with recurrent pancreatic ductal adenocarcinoma (PDAC).

Additional human imaging data of a Bicycle Imaging Agent (BIA) targeting EphA2 in patients with PDAC. The German Cancer Consortium (DKTK), part of a cooperative network with the German Cancer Research Center (DKFZ), presented human imaging data conducted with a Bicycle molecule targeting EphA2 labelled with gallium-68 (EphA2 BIA). Seven patients with histologically confirmed PDAC underwent PET/CT imaging up to three hours post injection of the EphA2 BIA. Data demonstrated rapid tumor uptake and excretion primarily via the kidneys in six out of seven patients. EphA2 BIA PET imaging successfully detected multiple liver, bone, lymph node, and peritoneal metastases.

These data are representative of the results seen in 15 out of 18 patients with PDAC who have undergone EphA2 BIA imaging to date. Bicycle Therapeutics believes these data validate the potential of EphA2 as a novel target in the treatment of cancer, demonstrate the translatability of preclinical data and highlight the potential of Bicycle molecules for targeted radioligand therapies and radiopharmaceutical imaging.
Preclinical assessment of nuzefatide anti-tumor activity in patient-derived xenograft (PDX) models of PDAC. Expression of EphA2 was found in all 16 PDAC PDX models. Of the 14 PDAC PDX models assessed for anti-tumor activity, 10 models were sensitive to nuzefatide, six of which showed high sensitivity. These data support the potential for nuzefatide to offer a novel option for the treatment of patients with PDAC.

In March 2026, Bicycle Therapeutics began enrolling patients in a Phase 2 clinical trial to evaluate efficacy, safety, and pharmacokinetics of nuzefatide in adult patients with recurrent PDAC, and the first patient was successfully dosed in April 2026.
Preclinical assessment of nuzefatide anti-tumor activity in cell-line-derived xenograft (CDX) models of head and neck squamous cell carcinoma (HNSCC). Nuzefatide demonstrated potent preclinical anti-tumor activity in EphA2-expressing CDX models of HNSCC.
The presentations are available in the Publications section of the Bicycle Therapeutics website.

(Press release, Bicycle Therapeutics, APR 20, 2026, View Source [SID1234664536])

On April 20, 2026, Arcus Biosciences, Inc. (the "Company") reported the discontinuation of the Phase 3 STAR-121 study, which is being conducted in collaboration with Gilead Sciences, Inc. ("Gilead"), due to futility. STAR-121 evaluated the anti-TIGIT antibody domvanalimab plus anti-PD-1 antibody zimberelimab and chemotherapy versus pembrolizumab plus chemotherapy as a first-line treatment for metastatic non-small cell lung cancer. The decision is based on the recommendation from the Independent Data Monitoring Committee ("IDMC"), following its review of data from a pre-planned futility analysis. Safety was not assessed at this futility analysis; however, no new safety issues have been identified during regular reviews by the IDMC.

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The STAR-121 study also evaluated zimberelimab and chemotherapy as an exploratory endpoint. Zimberelimab plus chemotherapy performed consistently with respect to overall survival as compared to pembrolizumab plus chemotherapy.

STAR-121, along with the Phase 2 EDGE-Lung study, will be discontinued. Gilead is communicating with investigators to determine appropriate next steps for patients in these studies.

Gilead Collaboration Update.

On April 20, 2026, the Company announced that the period for Gilead’s option rights under the Option, License and Collaboration Agreement entered into between the Company and Gilead in 2020, as amended, will end on July 14, 2026, following Gilead’s decision to not make the option continuation payment to the Company. Accordingly, Gilead will not have option rights to additional programs in the Company’s early-stage pipeline, including the CCR6, CD89 and CD40L programs, but will maintain its existing time-limited options to programs including AB801 (an investigational small molecule AXL inhibitor), AB598 (an investigational anti-CD39 monoclonal antibody), AB102 (an investigational MRGPRX2 antagonist), and an investigational TNF small molecule inhibitor.

The Company has full rights to casdatifan and the casdatifan development program, other than those rights licensed to Taiho in Japan and certain other Asian territories (not including China).

(Press release, Arcus Biosciences, APR 20, 2026, View Source [SID1234664534])

On April 20, 2026 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products, reported upcoming presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 17-22, 2026, in San Diego, Calif.

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Allogene’s presentations at AACR (Free AACR Whitepaper) highlight the potential of allogeneic CAR T to expand access, simplify delivery, and enable broader application of cell therapy across diseases when its inherent advantages are fully leveraged. The Company will participate in several AACR (Free AACR Whitepaper) 2026 scientific forums, including:

Poster: Preclinical Evaluation of Allogeneic BCMA/CD70 Dual CAR T Cells for High-Risk Multiple Myeloma
Presenter: Mark K. O’Dair, PhD, Allogene
Session Title: CAR T Cell Targets and TME Reprogramming
Poster Number: 1535
Location: Poster Section 7, Board 17
Session Date and Time: Monday, April 20, 9:00am-12:00pm PT

Based on its foundational work in oncology, Allogene is extending its Dagger technology into autoimmune disease, applying its gene-edited, dual-targeting CAR T approach to target both BCMA and CD70 on malignant plasma cells as well as selectively eliminate alloreactive immune cells to promote durable persistence with reduced need for chemotherapy-based lymphodepletion. This strategy builds on the Company’s expertise in allogeneic cell therapy in advanced renal cell carcinoma and is designed to deliver a readily available, off-the-shelf treatment with the potential to transform how both cancer and autoimmune diseases are treated.

Major Symposium: Off-the-Shelf Cell Therapies for Cancer and Beyond
Presenter: David Chang, M.D., Ph.D., President, CEO and Co-Founder, Allogene Therapeutics
Title: Allogeneic CAR-T: Science at Scale (SY13-03)
Location: Room 28 – Upper Level – Convention Center
Session Date and Time: Tuesday, April 21, 12:30-2:00pm PT

The future of CAR T will be defined by its ability to reach more patients, more reliably and earlier in the course of disease. Allogene’s allogeneic approach is designed to unlock this potential across five key dimensions: speed, with on-demand availability; safety, manageable across care settings; simplicity, as a one-time outpatient treatment; scalability, enabling broad patient access; and survival, with the potential to deliver meaningful clinical outcomes. Together, these attributes represent a path toward making CAR T a more practical and widely accessible therapy.

Forum: Cell Therapy at a Crossroads: Exploring the Evolving Landscape between Autologous, Allogeneic, and In Vivo Engineering (Session: FO06)
Presenter: Zachary Roberts, M.D., Ph.D., EVP, Research and Development, CMO, Allogene Therapeutics
Location: Ballroom 20 AB – Upper Level – Convention Center
Session Date and Time: Tuesday, April 21, 5:00pm-6:30pm PT

Allogeneic CAR T therapy represents a major step forward in the evolution from autologous products. With extensive experience across both hematologic and solid tumors, Allogene has been a singular leader since the earliest days of allogeneic cell therapy and has defined a path through many of the scientific challenges the field has faced. As key trials advance Allogene is positioning allogeneic CAR T as a bridge to biologic-like manufacturing scale necessary to address an ever-growing patient demand for these life-saving products.

(Press release, Allogene, APR 20, 2026, View Source [SID1234664533])

On April 20, 2026 Alligator Bioscience (Nasdaq Stockholm: ATORX), a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs, reported that new data from a Phase 1 investigator‑initiated trial evaluating intratumoral mitazalimab administered in conjunction with irreversible electroporation (IRE) in locally advanced pancreatic ductal adenocarcinoma (PDAC) will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026. The meeting takes place between 17-22 April 2026, in San Diego, California.

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The abstract reports updated immunological findings from the ongoing Phase 1 dose‑escalation study (NCT06205849). The study assesses mitazalimab when injected directly into the tumor at the time of surgical IRE in patients with locally advanced PDAC after standard-of-care chemotherapy.

The abstract highlights that all six patients with completed pre‑ and post‑treatment analyses demonstrated T‑cell reactivity to patient‑specific neoantigens. Overall, neoantigen reactivity increased significantly following treatment, indicating that mitazalimab + IRE results in an expansion of tumor specific T cells.

"Scientific interest in mitazalimab continues to grow, not least through the momentum we see in our investigator-initiated trials," said Søren Bregenholt, CEO of Alligator Bioscience. "The data presented at AACR (Free AACR Whitepaper) provide further evidence of the mechanistic potential of CD40 agonism to enhance antitumor immunity, even in difficult-to-treat cancers such as pancreatic cancer. We greatly value the engagement from leading academic centers who are exploring mitazalimab in innovative clinical settings, reflecting the continued confidence in its therapeutic promise."
Abstract details
Title: Irreversible electroporation (IRE) with intratumoral CD40 antibody increases T cell reactivity to personalized neoantigens in locally advanced pancreatic cancer
Time: Monday, 20 April 2026, 09:00 am – 12:00 pm PDT
Session: PO.CTP01.01 – Phase I Clinical Trials in Progress, Section 51
Presenter: Dr. Rebekah R. White, UC San Diego School of Medicine, La Jolla, CA

The accepted abstract is available at aacr.org.

(Press release, Alligator Bioscience, APR 20, 2026, View Source [SID1234664532])

On April 20, 2026 Akari Therapeutics, Plc (Nasdaq: AKTX), an oncology biotechnology company developing antibody drug conjugates (ADCs) with a novel RNA splicing modulator payload, reported the presentation of positive preclinical data for its lead TROP2-targeting ADC, AKTX-101, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026. Access the poster here.

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Unlike current TROP2-targeting ADCs that use Topoisomerase I Inhibitor (Inh.) payloads, AKTX-101 has the potential to address resistance to Topoisomerase I Inh. ADCs and contribute to durable anti-tumor efficacy due to the payload’s unique cytotoxic and immune-activating mechanisms of action.

The preclinical data compares the performance of AKTX-101 versus TROP2 ADCs with Topoisomerase I Inh. payloads in the killing of different cancer types driven by different cancer genes (oncogenes). AKTX-101’s ability to kill cancer cells at lower concentrations vs. TROP2 ADCs using Topoisomerase I Inh. payloads suggests that AKTX-101 is a more potent drug.

The preclinical data was published recently as an abstract in Cancer Research, an AACR (Free AACR Whitepaper) journal.

Here, AKTX-101 demonstrated greater potency and/or greater maximum cancer cell killing relative to TROP2 ADC Topoisomerase I Inh. payloads in cancers of the bladder, lung and breast. AKTX-101 demonstrated sub-nanomolar potency in all bladder cancer lines tested, a key tumor in which first-in-human clinical trials for AKTX-101 are planned.

AKTX-101 also demonstrated sub-nanomolar potency in several non-small cell lung cancer cell lines driven by EGFR, BRAF, and SMARCA4, as well as potent cell killing in HER2 breast cancer cell lines with inherent resistance to Topoisomerase I Inh. ADCs such as trastuzumab deruxtecan (ENHERTU).

"These data represent a significant step forward for our lead program, AKTX-101, and reinforce our belief that a differentiated ADC payload with multiple mechanisms of action has the potential to meaningfully improve outcomes for patients with TROP2-expressing cancers," commented Satyajit K. Mitra, Ph.D., Head of Oncology Research and Development at Akari Therapeutics. "We are seeing preclinical superior AKTX-101 potency and activity as compared to TROP2 ADCs using Topoisomerase I inhibitor payloads in bladder, lung, and breast cancer models. Together, these findings show that AKTX-101 has strong potential for targeting a broad range of cancer tumors and sub-types with superior cytotoxicity than current TROP2 ADCs that use Topoisomerase I Inhibitor payloads."

The TROP2 ADC class continues to emerge in terms of its potential, with revenue projections expected to reach ~$12B or greater by 2033 based on current and future entrants. Akari believes that AKTX-101, with its novel RNA splicing modulator payload, can grow this class further by addressing multiple solid tumors where TROP2 is overexpressed including bladder, lung, breast, pancreatic, head and neck, and others.

Key AKTX-101 Data Presented at AACR (Free AACR Whitepaper) Highlights:

AKTX-101 demonstrated strong, single-agent anti-tumor activity across multiple models across bladder, lung, and breast cancers.
AKTX-101 demonstrated greater potency and cell killing compared to current TROP2 ADCs, including Topoisomerase I inhibitor-resistant tumor models, as well as standard-of-care chemotherapies and targeted therapies. Combination of AKTX-101 with anti-PD-1 therapy resulted in synergistic anti-tumor efficacy and tumor regressions within in vivo models, supporting future combinations with checkpoint inhibition to maximize tumor remissions rates.
Broad in vitro cytotoxicitywas observed across a diverse panel of tumor models, including those with clinically oncogenic driver mutations including FGFR3, BRAF, EGFR, and SMARCA4.
Abizer Gaslightwala, CEO of Akari Therapeutics, added, "This data continues to add to the conviction and differentiation we have in our novel ADC payload PH1 targeting RNA splicing. We are focused on rapidly advancing AKTX-101 into the clinic, with IND-enabling studies underway and plans to submit an IND in the fourth quarter of 2026, followed by initiation of a Phase 1 study in the first quarter of 2027. Our team is executing against a clear development plan designed to efficiently translate these encouraging preclinical findings into clinical proof of concept."

These data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026. Access the poster here.

(Press release, Akari Therapeutics, APR 20, 2026, View Source [SID1234664531])