On April 22, 2026 Rakovina Therapeutics Inc. (TSX-V: RKV; FSE: 7JO0), a biopharmaceutical company advancing innovative cancer therapies through artificial intelligence (AI)-powered drug discovery, reported the presentation of new preclinical data from two of its lead programs at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held April 17–22 in San Diego, California.

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The data, presented across two poster sessions at the world’s premier cancer research forum, advance Rakovina’s AI-driven pipeline targeting DNA damage response (DDR) vulnerabilities in hard-to-treat solid tumors. Both programs leverage generative AI platforms to address longstanding limitations of existing cancer therapies, including poor central nervous system (CNS) penetrance and the toxicity burden of drug combination regimens.

Novel Brain-Penetrant Dual ATR-mTOR Inhibitor Demonstrates In Vivo Efficacy in PTEN-Deficient Cancers

The first poster, titled A Novel Brain-Penetrant Dual ATR-mTOR Inhibitor for PTEN-Deficient Cancers (Presentation #1743, DNA Damage and Repair 2 session, April 20), presented preclinical data from Rakovina’s program to develop first-in-class CNS-penetrating molecules that simultaneously inhibit ATR and mTOR, two key drivers of survival in PTEN-deficient cancer cells. The program was developed in collaboration with Variational AI (Vancouver, BC) using the Enki generative AI platform.

PTEN deficiency is found in up to 40% of gliomas and 63% of breast cancers, which frequently metastasize to the brain. Simultaneous inhibition of ATR and mTOR is a rational therapeutic strategy in PTEN-deficient tumors, as PTEN loss activates both ATR-dependent DNA damage signaling and mTOR-driven cell survival pathways. However, no approved therapy directly addresses this dual vulnerability with effective CNS penetrance.

Using the Enki latent diffusion model to simultaneously optimize potency, selectivity, CNS penetrance, and ADMET properties, Rakovina generated and synthesized a curated set of novel small-molecule dual ATR-mTOR inhibitor candidates. Key findings presented at AACR (Free AACR Whitepaper) 2026 include:

Enzymatic potency: Candidate compounds demonstrated equal or greater inhibition of recombinant ATR and mTOR enzymes compared to reference compounds ceralasertib and tuvusertib.
Selectivity: Candidates are equally or more selective against PIKK family enzymes than the reference compounds ceralasertib and tuvusertib.
Cell viability inhibition: Candidates inhibit cell viability of D283 medulloblastoma cells equally or more than reference compounds. A prototype lead candidate inhibited cell viability of both PTEN wild-type and PTEN-deficient cancer cell lines.
Metabolic stability: After 45 minutes of incubation with human liver microsomes, candidate compounds demonstrated strong metabolic stability.
CNS penetrance: Pharmacokinetic profiling following intraperitoneal administration in mice confirmed varying but measurable levels of CNS penetrance across candidates, with brain-to-plasma ratios broadly consistent with Enki AI predictions.
In vivo efficacy: In a subcutaneous LNCaP prostate tumor model, a prototype lead candidate significantly prolonged tumor doubling time compared to vehicle control, with equal potency to reference compound ceralasertib. Critically, the Rakovina candidate was better tolerated than ceralasertib, demonstrating less weight loss with daily dosing and no signs of hematological toxicity at terminal complete blood count analysis.
Optimization of candidate inhibitors is ongoing.

Novel AI-Designed Lipid Nanoparticle Formulation of kt-3283 Successfully Characterized

The second poster, titled Development of a Lipid Nanoparticle Formulation of the Bifunctional PARP and HDAC Inhibitor Kt-3283 (Presentation #6373, Drug Delivery session, April 21), presented preclinical formulation data on pLNP/kt-3283, developed in collaboration with NanoPalm (Riyadh, Saudi Arabia) using the EnsaliX AI platform.

kt-3283 integrates PARP inhibition and HDAC-mediated chromatin remodeling into a single compound, thereby improving the PARP efficacy, and eliminating the need for combination drug regimens and their associated toxicity risks. While kt-3283 has demonstrated potent anti-tumor activity across multiple tumor types in prior in vitro studies, its clinical viability has been limited by bioavailability and metabolic stability challenges. The pLNP formulation has been specifically designed to address these limitations.

Data presented confirm the successful assembly of the EnsaliX-designed patterned lipid nanoparticles. Physicochemical characterization confirmed uniform particle size, stable colloidal behavior, and a structured surface texture predicted to enhance cellular uptake. The pLNP/kt-3283 formulation demonstrated structure and particle size consistency supporting further biological evaluation.

Next steps include in vitro and in vivo characterization to confirm activity against PARP and HDAC enzymes, determine ADME properties, and evaluate efficacy in tumor models.

"Presenting at AACR (Free AACR Whitepaper) is a meaningful milestone for our team, and these results represent a genuine step forward for both programs," said Kim Oishi, Chief Executive Officer of Rakovina Therapeutics. "The in vivo efficacy data for our ATR-mTOR inhibitor are particularly encouraging. The compound demonstrated potency comparable to an established reference compound while exhibiting a meaningfully improved tolerability profile. That is exactly the differentiation we are building toward. Combined with the initial characterization of our LNP formulation for kt-3283, we believe these results reinforce the potential of our AI-driven pipeline and support a path toward IND-enabling studies."

Rakovina’s AI-powered discovery approach leverages generative AI platforms to evaluate billions of potential drug candidates at a pace not achievable through traditional methods. These capabilities are supported by the company’s access to the University of British Columbia’s lab infrastructure, enabling rapid in-house testing of lead compounds.

"These results demonstrate that our strategy of integrating AI-guided design with biological validation, is working as intended," said Dr. Mads Daugaard, President and Chief Scientific Officer of Rakovina Therapeutics. "For the ATR-mTOR program, our candidate inhibitors are tracking closely with the AI predictions for potency, selectivity, and CNS penetrance and our in vivo results give confidence in the direction of this program. For kt-3283, we have demonstrated that the EnsaliX-designed LNP formulation produces a well-characterized nanoparticle. The structured surface and organized phospholipid assembly we observed are precisely the properties expected to enhance nanoparticle stability and cellular uptake of kt-3283. Both programs have clear next steps, and we are moving forward with purpose."

The data presented at AACR (Free AACR Whitepaper) 2026 reinforce the progress of Rakovina’s AI-enabled DDR inhibitor pipeline and inform the next phase of preclinical development for both programs. For the ATR-mTOR program, further optimization of candidate inhibitors is ongoing. For the kt-3283 LNP program, the company will advance in vitro and in vivo studies to further characterize biological activity prior to evaluating efficacy in tumor models.

Rakovina intends to use these findings to advance best-in-class lead candidates toward IND-enabling studies in collaboration with pharmaceutical partners.

(Press release, Rakovina Therapeutics, APR 22, 2026, View Source [SID1234664716])

On April 22, 2026 BeyondSpring Inc. (NASDAQ: BYSI) reported new preclinical data at the 2026 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) demonstrating that Plinabulin has the potential to enhance both the efficacy and tolerability of ADC therapy — potentially boosting anticancer responses while keeping patients on treatment long enough to benefit.

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Antibody-drug conjugates — a form of targeted chemotherapy that delivers cancer-killing agents directly to tumor cells, known as ADCs — have emerged as one of oncology’s most important new treatment classes. But two persistent clinical barriers limit their full potential: they do not always produce durable responses, and neutropenia (a dangerous drop in white blood cell counts) can force dose reductions or treatment delays that cut treatment short. New AACR (Free AACR Whitepaper) data show that Plinabulin directly and simultaneously addresses both.

Three Key Findings from AACR (Free AACR Whitepaper) 2026

The data show why the combination works. Plinabulin, when added to two leading approved ADCs — T-DXd (trastuzumab deruxtecan) and Dato-DXd (datopotamab deruxtecan) — produced three significant results that neither drug achieved alone:

Stronger anticancer activity: Complete tumor regressions were more frequent and animals survived significantly longer — in both two-drug (ADC+ Plinabulin) and three-drug (ADC+ Plinabulin + PD-1 inhibitor) combinations (PD-1 inhibitors are immunotherapies that activate the body’s own immune system to fight cancer).
Better tolerability to potentially keep patients on therapy: Plinabulin reduced animal death in both two-drug and three-drug combinations. In 6 prior clinical studies, Plinabulin measurably reduced chemotherapy-induced neutropenia, the white blood cell toxicity that commonly forces ADC dose reductions or treatment delays — potentially allowing patients to remain on treatment long enough to benefit from the drug’s anticancer activity.
Immune system activation: Analysis showed that Plinabulin enhanced the body’s own cancer-fighting T-cells, significantly increasing CD8+ T cell/Treg ratio — providing a biological explanation for why the combination outperforms either drug alone.

Plinabulin is Mechanistically Complementary, Not Merely Additive

Plinabulin activates a protein called GEF-H1 that simultaneously matures immune cells (dendritic cells) to attack tumors, signals the body to replenish cancer-fighting blood cells, and disrupts the blood supply feeding tumors. These are precisely the biological pathways that ADCs do not activate — which is why the two work better together than either does alone.

In BeyondSpring’s pivotal Phase 3 DUBLIN-3 study (The Lancet Respiratory Medicine, 2024), Plinabulin combined with docetaxel chemotherapy doubled two- and three-year survival rates in second- and third-line EGFR wild-type NSCLC patients — and simultaneously reduced docetaxel-limiting grade 4 neutropenia from 33% to 5%, keeping patients on therapy longer for the drug to work. The new AACR (Free AACR Whitepaper) data extend that same combination logic into the ADC setting, broadening Plinabulin’s reach across the treatment landscape.

BeyondSpring’s planned DUBLIN-4 program — a 442-patient FDA-aligned confirmatory Phase 3 trial building directly on the DUBLIN-3 results — is the defined next clinical step. Today’s AACR (Free AACR Whitepaper) data further strengthen the scientific rationale for Plinabulin’s combination potential and point toward future ADC combination studies beyond the confirmatory program.

Plinabulin as a Potential Backbone Drug Across Multiple ADC Combinations

ADCs are increasingly being tested in earlier lines of cancer treatment and in combination with immunotherapy. However, recent large Phase 3 studies — TROPION-Lung01 and EVOKE-01 — showed that leading ADCs failed to outperform older chemotherapy, such as docetaxel, in certain lung cancer settings, underscoring the need for an agent that can improve the efficacy and tolerability of ADC-based combinations.

Plinabulin’s ability to simultaneously boost efficacy and reduce toxicity positions it as a potential backbone agent across the ADC landscape — a role no other drug currently fills. Today’s AACR (Free AACR Whitepaper) data open the door to ADC combination studies as a natural next chapter in Plinabulin’s clinical development, alongside the ongoing DUBLIN-4 confirmatory program.

"Plinabulin has the potential to enable ADC therapy to deliver on its full promise — producing more complete responses, extending survival, and keeping patients on treatment. These AACR (Free AACR Whitepaper) data further strengthen our conviction in Plinabulin’s combination potential, as we advance the DUBLIN-4 confirmatory Phase 3 program in NSCLC post immune checkpoint inhibitors and explore the broader opportunity in ADC-based regimens."
— Dr. Lan Huang, Co-Founder, Chairman, and CEO, BeyondSpring Inc.

BeyondSpring’s China operations have been a strategic engine in building the ADC partnerships that support Plinabulin’s global development.

"China’s ADC research ecosystem is among the most active in the world, and BeyondSpring is well-positioned to leverage those capabilities. Our collaboration with Shanghai Chest Hospital demonstrated the value of strategic partnerships in advancing Plinabulin’s preclinical and clinical development in ADC combination, and we see continued opportunity to build on that model as the ADC combination landscape evolves."
— Min Qiu, Deputy General Manager, BeyondSpring China

BeyondSpring’s AACR (Free AACR Whitepaper) 2026 Presentation

Title: Plinabulin Boosts Antitumor Efficacy of Topoisomerase Inhibitor-Based Antibody-Drug Conjugates Without or With Immune Checkpoint Inhibitor

Presenters: Yingjuan June Lu, Xiaoyan He, Weiwei Cheng, Zhengyan Zhang, James Tonra, Lan Huang

Session: T Cell Engagers 2 / Antibody-Drug Conjugates 1 (Immunology Track)

Poster Number: 5597

About Plinabulin

Plinabulin is a late-stage Phase 3 anticancer agent and first-in-class GEF-H1 (guanine nucleotide exchange factor H1) agonist. Its multifunctional mechanism — encompassing dendritic cell maturation, tumor microenvironment modulation, anti-angiogenesis, and chemotherapy-induced neutropenia (CIN) mitigation — activates biological pathways that standard chemotherapy and ADCs do not. Over 700 cancer patients have been treated with good tolerability and durable anticancer benefit in rational combination settings. DUBLIN-3 Phase 3 results in NSCLC were published in The Lancet Respiratory Medicine in 2024.

About DUBLIN-3 and the Path to DUBLIN-4

In the DUBLIN-3 Phase 3 study of 2L/3L EGFR wild-type NSCLC (Lancet Respiratory Medicine, 2024), Plinabulin plus docetaxel significantly outperformed docetaxel monotherapy (n=559, 1:1 randomization), with improvements in OS, PFS, and ORR; doubling of 2- and 3-year survival rates; and reduction of docetaxel-induced grade 4 neutropenia from 33% to 5% (p<0.0001).

DUBLIN-4 is BeyondSpring’s planned FDA-aligned confirmatory Phase 3 program (n=442, 1:1 randomization), designed to validate the DUBLIN-3 results in a prospective confirmatory setting in a patient population selected based on Plinabulin’s mechanism of action: non-squamous NSCLC patients who have progressed on PD-1/L1 inhibitors. The ADC preclinical data presented at AACR (Free AACR Whitepaper) 2026 broaden the scientific case for Plinabulin’s combination potential.

(Press release, BeyondSpring Pharmaceuticals, APR 22, 2026, View Source [SID1234664715])

On April 22, 2026 The US Food and Drug Administration (FDA) reported that it has extended by up to three months the target action date for its review of the biologics license application for Sarclisa (isatuximab-irfc) subcutaneous (SC) in combination with approved standard-of-care regimens for the treatment of patients with multiple myeloma (MM) across all currently approved US indications of Sarclisa intravenous (IV) formulation. The revised target action date for the FDA decision is July 23, 2026.

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Sanofi is committed to working closely with the FDA to bring this new advancement to patients and providers as quickly as possible. If approved, Sarclisa would be the first anticancer treatment to be administered through an on-body injector (OBI).

On March 26, 2026, the European Medicine Agency Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of Sarclisa SC administered via both an OBI and manual injection for the treatment of MM patients across all currently approved indications and combinations for Sarclisa IV formulation in the EU. A final decision is expected in the coming months.

About Sarclisa
Sarclisa (isatuximab-irfc) has been approved in almost 60 countries across four indications for certain patients with newly diagnosed MM and relapsed or refractory MM. Sarclisa-based regimens have been prescribed to treat more than 60,000 patients worldwide.

At Sanofi, we are building on a long-standing commitment to oncology as we continue to chase the miracles of science to improve the lives of those living with cancer. We are committed to transforming cancer care by developing innovative, first and best-in-class immunological and targeted therapies for rare and difficult-to-treat cancers with high unmet need.

For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov.

(Press release, Sanofi, APR 22, 2026, View Source [SID1234664714])

On April 22, 2026 BlossomHill Therapeutics, Inc., a privately-held, clinical-stage biopharmaceutical company applying an intentional, chemistry-based approach to develop innovative small molecule medicines for the treatment of cancer, reported new preclinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, highlighting the discovery and characterization of its lead pan-KRAS inhibitor, BH-501284, along with additional updates across its pipeline.

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"Despite recent advances, patients with KRAS-driven tumors continue to face limited and often short-lived treatment options. Our mini-symposium presentation at AACR (Free AACR Whitepaper) introduces our differentiated pan-KRAS inhibitor, BH-501284, with pre-clinical data demonstrating the potential for this molecule to deliver broad and durable pathway inhibition across multiple KRAS-driven tumors," said Jean Cui, Ph.D., Founder and Chief Executive Officer of BlossomHill Therapeutics. "We are particularly encouraged by the depth and consistency of activity observed across models, including sustained target engagement and tumor regression at low dose levels. Based on these results, we are advancing IND-enabling studies for BH-501284 and preparing for clinical development."

Data presented in the AACR (Free AACR Whitepaper) Mini Symposium provides pre-clinical data supporting BH-501284 as a novel, orally available, non-covalent, pseudo-irreversible pan-KRAS inhibitor designed to overcome limitations of current KRAS-targeted therapies.

Key findings from the mini symposium titled "Discovery and characterization of BH-501284: A non-covalent, pan-KRAS inhibitor for treatment of diverse KRAS-mutant tumors" include:

Median IC50 of 0.83 nM across 41 different G12/G13 KRAS mutant cell lines (excluding G12R), but sparing HRAS and NRAS (>650 nM) to avoid the toxicity of pan-RAS inhibitors
Picomolar binding affinity and prolonged residence time (>54 hours) mirroring the binding of covalent inhibitors but with a non-covalent, pseudo-irreversible chemistry leading to prolonged inhibition of KRAS signaling
Deep tumor regression in multiple KRAS-mutant xenograft models achieved at lower doses (5-15 mg/kg BID) compared to what has been reported with other contemporary Switch-II pocket inhibitors
The company also presented a poster describing the preclinical characterization of additional molecules within the pan-KRAS program (BH-501242, BH-501352), in which BH-501242 demonstrated cellular potency exceeding that of comparator molecules, and both molecules demonstrated prolonged non-covalent binding, and favorable absorption, distribution, metabolism and excretion (ADME) properties.

Additional AACR (Free AACR Whitepaper) Posters from the BlossomHill Therapeutics Pipeline

BH-30643 (Mutant-selective EGFR inhibitor)
Poster: "BH-30643, a novel macrocyclic non-covalent, mutant-selective EGFR inhibitor, addresses the resistance and potency limitations of contemporary EGFR TKIs"

Potent and durable inhibition across diverse EGFR-mutant models, including C797S and T790M
Maintained low nanomolar potency in presence of EGFR ligands
Showed prolonged suppression of tumor cell growth compared to approved EGFR TKIs
Induced deep tumor regression across multiple in vivo models, including intracranial models
Sustained suppression of EGFR signaling in dose- and time-dependent manner
Findings support potential of BH-30643 to overcome key limitations of current therapies
BH-30236 (CLK inhibitor for hematologic malignancies)
Poster: "CLK inhibitor BH-30236 synergizes with venetoclax in anti-leukemia activity via splicing modulation in preclinical AML and CLL models"

Broad anti-proliferative activity through modulated mRNA splicing
Reduced expression of pro-survival factors, leading to activation of apoptosis and DNA damage response pathways
Consistent synergy with venetoclax across multiple blood cancer models
Induced tumor regression in resistant acute myeloid leukemia (AML) xenografts, including complete responses
Sustained tumor-free survival following treatment discontinuation, consistent with effects on leukemia stem cell populations
Findings support continued clinical development of BH-30236 as both a monotherapy and in combination regimens

(Press release, BlossomHill Therapeutics, APR 22, 2026, View Source [SID1234664713])

On April 22, 2026 EvolveImmune Therapeutics, a clinical-stage immuno-oncology company developing a new class of multi-specific T cell engagers with integrated CD2 costimulation, reported the presentation of new data highlighting its novel EVOLVE T cell engager platform and an update on its lead asset, EVOLVE104, at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The results presented included findings from collaborative research conducted in partnership with Michael L. Dustin, Ph.D., Kennedy Trust Professor of Molecular Immunology at the University of Oxford, UK. The AACR (Free AACR Whitepaper) conference is being held April 17-22, 2026, in San Diego, California.

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The EVOLVE platform is designed to therapeutically co-opt key mechanisms central to efficient immune synapse formation and T cell effector function. This approach aims to bypass low tumor immunogenicity, conditionally activate adaptive immunity and reduce T cell dysfunction, allowing for amplified and sustained T cell tumor killing capacity, to address unmet medical needs in solid tumors and hematologic malignancies.

"Our presentations at AACR (Free AACR Whitepaper) share an impressive collection of first-in-class scientific findings for the EVOLVE platform and the continued clinical progress of our EVOLVE104 program. We are unlocking new insights into the mode of action of our EVOLVE platform which are catalyzing new and impactful prospects for our pipeline growth," said Stephen Bloch, M.D., Chief Executive Officer of EvolveImmune. "Our focus remains on efficiently executing our ongoing clinical study for EVOLVE104, while advancing further differentiated innovation opportunities for our EVOLVE technology."

Highlights from the company’s presentations at the AACR (Free AACR Whitepaper) conference are as follows:

EVOLVE104:

EvolveImmune spotlighted its ongoing phase 1 clinical trial of EVOLVE104, the first molecule from the company’s EVOLVE platform to enter clinical development (presentation #CT079). The compound targets a novel set of tumor-associated antigens, ULBP2/5/6, which are expressed on bladder cancers and squamous cell carcinomas. Notably, EVOLVE104 is the first T cell-redirecting therapeutic candidate targeting ULBP2/5/6 to enter clinical development.

The phase 1a/1b study, EIU-104101 (NCT07217171), is evaluating the safety, efficacy, pharmacokinetics and pharmacodynamics of EVOLVE104. The trial, began enrolling in December 2025, is designed with an initial phase 1a dose escalation portion, to be followed by phase 1b dose expansion, enrolling up to 160 subjects with locally advanced or metastatic bladder cancer and squamous cell carcinomas of the lung, esophagus, skin, tongue, and anogenital region who have relapsed from or are refractory to standard of care therapies. The study is currently open at nine US sites, with additional sites expected to open during the remainder of 2026.

EVOLVE T Cell Engager Platform:

In an oral minisymposium presentation (presentation #4055), EvolveImmune shared updated results from preclinical studies demonstrating that EVOLVE’s integrated CD2 co-stimulation approach shows superiority to conventional CD3-bispecific T cell engagers. Chronic in vitro human T cell stimulation with EVOLVE demonstrated sustained activation and proliferation, as well as enhanced differentiation into more effective effector-memory T cells. This activity correlated with improved tumor-dependent cytotoxicity compared to conventional CD3-bispecific T cell engagers. Notably, this superior profile for EVOLVE was observed with primary human tumor-infiltrating lymphocytes as well.

The enhanced T cell activity driven by EVOLVE led to greater tumor growth inhibition in an in vivo lung tumor xenograft model, when compared to bispecific T cell engagers. These findings add to the growing collection of evidence demonstrating that integrated T cell CD2 costimulation mediated by EVOLVE molecules results in superior human T cell performance compared to conventional CD3-bispecific T cell engagers.

A second poster presentation (presentation #5594) described experimental results conducted in collaboration with the laboratory of Professor Dustin. These findings showed that the EVOLVE platform functionally mimics the naturally occurring processes involved in human T cell recognition of target cells for their activation. This includes the active generation of an immune interface, or immune synapse, between T cells and target cells, which includes the positioning of CD2 to the corolla of the synapse, a hallmark feature of this interface. This activity correlated with increased T cell receptor signaling, improved T cell fitness and greater tumor killing. These findings provide further insight into the fundamental mechanistic activity that mediates the ability of EVOLVE to enhance T cell-mediated anti-tumor activity.

"It is remarkable how well EVOLVE mimics synaptic patterns generated by natural CD58 in a target membrane," said Professor Dustin.

About EVOLVE104
EVOLVE104 is a next-generation trispecific T cell engager that binds CD3 and CD2 on T cells and the tumor-associated antigens ULBP2/5/6, which have limited expression in normal human tissues and are found on a number of epithelial-derived malignancies, including urothelial carcinoma and a broad array of squamous cell carcinomas. In preclinical studies, EVOLVE104 has demonstrated compelling single-agent activity and combination activity with anti-PD-1 therapy, the ability to reinvigorate dysfunctional T cells, and a promising safety profile. EVOLVE104 is currently being studied in a first-in-human phase 1 clinical trial in subjects with advanced, relapsed or refractory solid tumors (NCT07217171).

(Press release, EvolveImmune Therapeutics, APR 22, 2026, View Source [SID1234664712])