C4 Therapeutics Announces First Patient Dosed in Phase 1b Trial of Cemsidomide in Combination with Elranatamab (ELREXFIO®) for Relapsed/Refractory Multiple Myeloma

On March 25, 2026 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported that the first patient has been dosed with cemsidomide, an oral IKZF1/3 degrader, in a Phase 1b trial evaluating cemsidomide and dexamethasone in combination with elranatamab (ELREXFIO), an FDA-approved B-cell maturation antigen CD3 targeted bispecific antibody, for the treatment of relapsed/refractory multiple myeloma (RRMM).

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"Data from our Phase 1 trial support cemsidomide as a potential best-in-class, next-generation IKZF1/3 degrader and the initiation of this Phase 1b trial, along with our late-line Phase 2 MOMENTUM trial, enable an efficient path toward bringing cemsidomide to growing myeloma patient populations across multiple lines of therapy," said Len Reyno, M.D., chief medical officer of C4 Therapeutics. "Bispecific T-cell engagers have quickly become a critical treatment pillar in multiple myeloma while IKZF1/3 degraders remain foundational therapies across multiple lines and combination regimens in multiple myeloma. In this combination with elranatamab, we see an opportunity to leverage cemsidomide’s potent direct anti-myeloma effect and its ability to enhance the immune environment which has the potential to deliver a deeper and more durable therapeutic response for patients, including those in earlier lines of therapy."

The Phase 1b trial is an open-label, multicenter study to establish an optimal dose for cemsidomide in combination with elranatamab by evaluating the safety and tolerability as well as preliminary anti-myeloma activity of cemsidomide in combination with elranatamab in RRMM patients. The trial will enroll up to 54 patients to evaluate cemsidomide in combination with elranatamab, beginning at the 75 µg dose of cemsidomide with the opportunity to explore 50 µg and 100 µg doses of cemsidomide. The primary endpoint is to assess the safety and tolerability of cemsidomide in combination with elranatamab. Secondary endpoints will evaluate anti-myeloma activity per the International Myeloma Working Group (IMWG) response criteria, which will include the overall response rate, minimal-residual disease (MRD)-negative complete response rate, duration of response and other relevant measures. In October 2025, C4T and Pfizer entered into a clinical trial collaboration supply agreement under which Pfizer provides elranatamab at no cost while C4T sponsors and conducts the clinical trial. Phase 1b data from all cohorts evaluating cemsidomide in combination with elranatamab is anticipated in mid-2027.

The Phase 1b trial is part of a broader developmental strategy to support cemsidomide’s use across multiple lines of treatment. This strategy also includes the ongoing Phase 2 MOMENTUM Trial investigating the use of cemsidomide and dexamethasone in the fourth line of treatment or later. In addition to these two trials, C4T intends to evaluate cemsidomide in combination with other anti-myeloma agents, and remains on track to share these plans in mid-2026.

About Cemsidomide
Cemsidomide is an investigational, orally bioavailable molecular glue degrader (MonoDAC degrader) of IKZF1/3, transcription factors foundational to multiple myeloma biology. Data from the Phase 1 trial, which has completed enrollment, show cemsidomide’s differentiated safety and tolerability profile and potentially class-leading anti-myeloma activity that support the potential for durable outcomes.

About Cemsidomide in Combination with Elranatamab (ELREXFIO)
The Phase 1b trial is designed to evaluate the safety, tolerability and preliminary efficacy of cemsidomide and dexamethasone in combination with elranatamab, an FDA-approved B-cell maturation antigen CD3 targeted bispecific antibody. Data generated from the cemsidomide Phase 1 trial in relapsed/refractory multiple myeloma demonstrate robust T-cell activation and cytokine expression across multiple doses. By activating immune T-cells, cemsidomide, when combined with a BCMAxCD3 bispecific such as elranatamab, may amplify the anti-myeloma immune response and lead to deeper and more durable responses. The study will evaluate different cemsidomide dose levels (beginning with 75 µg, with the opportunity to simultaneously explore 50 µg and 100 µg) in patients who have received one to four prior lines of therapy, which must have consisted of at least one IKZF1/3 degrader. Exclusion criteria for patients include those who have received prior treatment with a BCMA-directed T-cell engager or BCMA-directed CAR-T therapy. More information is available at clinicaltrials.gov (NCT07280013).

About the MOMENTUM Trial
MOMENTUM (Multi-center trial Of cemsidoMidE iN relapsed/refracTory mUltiple Myeloma) is a Phase 2, open-label, single-arm, study to evaluate efficacy, safety, pharmacokinetics and pharmacodynamics of cemsidomide in combination with dexamethasone in patients with relapsed/refractory multiple myeloma. Data from the Phase 1 trial identified 100 µg as the recommended Phase 2 dose. The primary endpoint is overall response rate per International Myeloma Working Group response criteria, as assessed by an independent review committee. Approximately 100 patients who have received at least three prior anti-myeloma regimens that must have included an IKZF1/3 degrader, a proteasome inhibitor, an anti-CD38 antibody, and a T-cell engager or CAR-T therapy will be enrolled in the trial. More information is available at clinicaltrials.gov (NCT07284758).

About Multiple Myeloma
Multiple myeloma (MM) is a rare blood cancer affecting plasma cells. Approximately 36,000 people in the United States are diagnosed with MM each year. Approved IKZF1/3 degraders remain foundational therapies across lines of MM treatment. Despite advances, including immune-directed approaches, most patients ultimately relapse, underscoring a growing need for new therapeutics options that continue to leverage IKZF1/3 degradation to drive myeloma cell death and T-cell activation.

(Press release, C4 Therapeutics, MAR 25, 2026, View Source [SID1234663899])

BeyondSpring Reports 2025 Year-End Financial Results

On March 25, 2026 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage company developing transformative therapies for the treatment of cancer and other diseases, reported its financial results for the year ended December 31, 2025, and highlighted late-stage clinical progress for Plinabulin and strategic developments related to its equity interest in SEED Therapeutics ("SEED").

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2025: Clinical and Operational Progress
"2025 was a year of important clinical and operational progress for BeyondSpring and SEED Therapeutics," said Dr. Lan Huang, Co-Founder, Chairman and Chief Executive Officer of BeyondSpring. "We advanced our Phase 3 Plinabulin program, generated meaningful clinical data, and strengthened our strategic and financial position."

"BeyondSpring made meaningful progress advancing Plinabulin in Phase 3 NSCLC, while SEED Therapeutics reached a critical milestone — initiating its first clinical trial following IND clearance in both the U.S. and China — and strengthened its leadership team and capital resources."

Positioned for 2026 and Beyond
"With a solid scientific and clinical foundation and clear regulatory pathways, we believe BeyondSpring and SEED are well positioned for the next stage of development," Dr. Huang concluded. "As we enter 2026, we remain focused on advancing the DUBLIN-4 confirmatory trial for Plinabulin in non-squamous EGFR wild-type NSCLC post immune checkpoint inhibitors, supporting SEED’s Phase 1a clinical program for ST-01156 in solid tumors, and creating long-term value for our shareholders."

Recent Clinical and Business Updates
Plinabulin Demonstrates Overall Survival Benefit in Phase 3 NSCLC Study; Confirmatory Trial Planned
There is a significant unmet need in EGFR wild-type NSCLC following immune checkpoint inhibitor (ICI) therapy, where numerous Phase 3 studies have failed to improve overall survival over standard of care docetaxel.

BeyondSpring reported positive Phase 3 results from the DUBLIN-3 study evaluating plinabulin in combination with docetaxel in second- and third-line (2/3L) EGFR wild-type non-small cell lung cancer (NSCLC). The study demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to docetaxel alone (ITT, n=559), with results published in The Lancet Respiratory Medicine.

At IASLC North America and ESMO (Free ESMO Whitepaper) Asia in December 2025, BeyondSpring presented updated data from the mechanism-targeted non-squamous NSCLC population (n=332; 24-month after database lock), in which the combination achieved:

OS hazard ratio (HR) of 0.72 (p=0.0078)
Median OS improvement of 2.5 months vs. docetaxel
Doubling of 2-year and 3-year survival rates
Favorable safety profile, reducing grade 4 neutropenia from >30% to 5% (p<0.0001)
To date, over 700 patients have been treated with plinabulin across clinical studies, supporting the characterization of its safety and tolerability profile.

Based on these findings and discussions with the U.S. FDA, BeyondSpring plans to initiate the global Phase 3 DUBLIN-4 confirmatory study, focusing on a mechanism-enriched patient population of EGFR wild-type non-squamous NSCLC progressed on prior PD-1/L1 inhibitors with overall survival as the primary endpoint (NCT07361484).

Plinabulin Shows Potential to Overcome PD-1/PD-L1 Resistance
Emerging clinical data suggests plinabulin may help address acquired resistance to PD-1/PD-L1 therapies — a major challenge affecting approximately 60% of patients, with limited therapies for these progressed patients. With PD-1/PD-L1 therapies representing a multi-billion-dollar market, addressing resistance remains one of the most significant opportunities in oncology.

Presentations at ASCO (Free ASCO Whitepaper) 2025 and SITC (Free SITC Whitepaper) 2025 on multiple early-stage and investigator-initiated studies of Plinabulin combinations:

Plinabulin + pembrolizumab + docetaxel (303 study, NCT05599789): A Phase 2 study conducted at Peking Union Hospital in China in metastatic NSCLC patients progressing on PD-1/PD-L1 inhibitors (n=47) demonstrated:
Median progression-free survival (PFS) of 7.0 months
Disease control rate (DCR) of 85% and overall response rate (ORR) of 18.2%
Median OS not reached with 24-month overall survival rate of 66%
Whole blood analysis indicated higher proportions of activated CD4+/CD8+ T-cells post treatment

Plinabulin + PD-1 inhibitor + radiation (NCT04902040): A Phase 1 study conducted at MD Anderson Cancer Center across eight tumor types resistant to checkpoint inhibitors showed:
DCR of 54% and ORR of 23%
Mechanistic evidence of dendritic cell maturation and immune activation
Identification of a potential predictive biomarker (GEF-H1 immune signature)
These findings, published in Med 2025 (Cell Press), support plinabulin’s proposed immune-priming mechanism and its potential role in combination strategies to restore tumor sensitivity to immunotherapy
BeyondSpring Business Update

In January 2025, BeyondSpring entered into definitive agreements to sell a portion of its Series A-1 Preferred Shares of SEED for gross proceeds of approximately $35.4 million to advance late-stage clinical development of Plinabulin. First closing of approximately $7.35 million was completed in February 2025.
SEED Therapeutics (Reported as Discontinued Operations) Advances First Clinical Program and Strengthens Organization
SEED Therapeutics continued to make progress in 2025 and early 2026, advancing its targeted protein degradation platform and pipeline.

Key highlights include:

ST-01156, a novel oral RBM39 degrader:
Received U.S. FDA Orphan Drug and Rare Pediatric Disease Designations
Achieved IND clearance in both the U.S. and China
Dosed first patient in a Phase 1a study in January 2026
ST-01156 Phase 1a enrolling at leading U.S. cancer centers: Dana-Farber, Massachusetts General Hospital, Memorial Sloan Kettering, MD Anderson Cancer Center, Hoag, and City of Hope
Presentation at AACR (Free AACR Whitepaper) 2025 on ST-01156 mechanism and preclinical studies including complete tumor regression in Ewing sarcoma and other cancer models; new degrader approaches in KRAS G12D degradation
SEED Business Update

Completed a $30 million Series A-3 financing
Appointed Dr. Bill Desmarais as Chief Financial Officer and Chief Business Officer
Named a finalist for the 2025 Prix Galien USA "Best Start-Up" Award
Full-Year 2025 Financial Resultsˆ
Continuing operations:

R&D expenses: $4.4 million (vs. $2.6 million in 2024), driven by increased drug manufacturing, NSCLC data management, Plinabulin combination research, regulatory consulting, and personnel costs
G&A expenses: $4.6 million (vs. $6.1 million in 2024), driven by lower personnel costs, reduced consulting expenses, and lower corporate overhead
Net loss: $8.7 million (vs. $8.9 million in 2024)
Cash, cash equivalents, and short-term investments: $12.6 million as of December 31, 2025
Discontinued operations:

Net loss: $5.5 million (vs. $7.8 million in 2024)
Current assets: $8.0 million as of December 31, 2025
Note 1. As a result of BeyondSpring entering into definitive agreements to sell a portion of its Series A-1 Preferred Shares of SEED, SEED’s operations met the criteria as discontinued operations under ASC 205-20 for financial reporting purposes.

(Press release, BeyondSpring Pharmaceuticals, MAR 25, 2026, View Source [SID1234663898])

Boehringer Ingelheim delivers on late-stage pipeline with two key launches, grows sales by 7.3%* in a successful 2025

On March 25, 2026 Boehringer Ingelheim reported about key launches in its Human Pharma business in 2025, bringing two medicines with FDA Breakthrough Therapy designation for lung cancer and pulmonary fibrosis to market in the second half of 2025. Group net sales rose by 7.3%* to EUR 27.8 billion for the full year, supported by both the Human Pharma and Animal Health business. In 2025, Boehringer increased Research and Development (R&D) investments to EUR 6.4 billion, representing 22.9% of group net sales. The company reached 70 million patients in 2025, delivering innovative medicines to more patients than ever before.

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"2025 reinforced the strength of our pipeline and underscored the impact of our long-term investment in R&D. With two newly launched medicines in oncology and respiratory, we are addressing high unmet medical needs of patients, while also driving the renewal of our portfolio. Our pipeline positions us well to continue to make a real difference across important disease areas, and to bring innovative therapies to more patients than ever," said Shashank Deshpande, Chairman of the Board of Managing Directors and responsible for Human Pharma. "As 2026 unfolds with pivotal Phase III programs and readouts as well as new launches ahead, we strive to improve the lives of patients, animals, and communities worldwide."

Frank Hübler, Member of the Board of Managing Directors responsible for Finance, added: "In volatile markets and amid regional challenges, our business proved resilient as we focused on what we do best: bringing more medicines to patients and animals. We are investing more than ever in innovation, which reflects our ambition for the next years."

Human Pharma: JARDIANCE (empagliflozin) and OFEV (nintedanib) continue to grow; HERNEXEOS and JASCAYD launched

Human Pharma sales rose 7.4%* to EUR 22.7 billion, supported by strong performance in its core brands. JARDIANCE, for the treatment of chronic kidney disease, type 2 diabetes and heart failure, grew 8.7%* to EUR 8.8 billion. Sales for OFEV, used to treat idiopathic pulmonary fibrosis and other progressive fibrosing interstitial lung diseases, increased 5.4%* to EUR 3.8 billion.

Boehringer Ingelheim expanded its portfolio with the launch of two innovative therapies in 2025: HERNEXEOS, an oral treatment for HER2-mutant advanced non-small cell lung cancer, was launched in the U.S. in August 2025. The company also launched JASCAYD, which was approved in the U.S. and China for idiopathic pulmonary fibrosis (IPF) in October 2025, and for progressive pulmonary fibrosis (PPF) in December 2025. JASCAYD represents the first new innovative therapy for IPF coming to market in more than a decade.

Human Pharma R&D investments came in at EUR 5.8 billion or 27.4% of the unit’s net sales. The company continued to advance its pipeline across cardiovascular, renal and metabolic diseases (CRM), oncology, respiratory and immunology, mental health, and eye health. The pipeline today includes more than 80 projects, representing over 50 new molecular entities. Ongoing advances in Boehringer’s growing mid‑ and late‑stage pipeline are building towards a sustained wave of potential launches, positioning the company to deliver transformative impact for patients in the years to come.

Animal Health: preventing the spread of transboundary animal diseases

In 2025, the Animal Health business demonstrated resilience and impact, with sales rising 6.5%* to EUR 4.9 billion. Growth was driven by pet parasiticides and therapeutics, poultry, and ruminant segments, with NEXGARD growing 8.5%* to EUR 1.4 billion, cementing its position as the industry’s top-selling parasiticide brand.

The company worked side by side with farmers, veterinarians, and governments, to help combat livestock diseases such as avian influenza, foot-and-mouth disease, and bluetongue virus. Boehringer received EU Marketing Authorization under Exceptional Circumstances for two poultry vaccines, supporting producers in keeping their poultry flocks healthy and increasing preparedness for avian influenza outbreaks. In addition to the VAXXINACT H5 avian influenza vaccine, VAXXITEK HVT+IBD+H5 is a new trivalent vaccine protecting chickens and turkeys against Marek’s disease, Infectious Bursal Disease and H5 avian influenza.

Outlook

In 2026, Boehringer expects to build on the momentum of recent years with continued progress across the Animal Health and Human Pharma pipelines and critical inflection points particularly in CRM, oncology and eye health.

(Press release, Boehringer Ingelheim, MAR 25, 2026, View Source [SID1234663883])

Clarity signs a large-scale Manufacturing Supply Agreement for copper-64 with Theragenics

On March 25, 2026 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for patients with cancer, reported the signing of a large-scale Manufacturing Supply Agreement for copper-64 with Theragenics.

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The agreement relates to Theragenics’ 134,000 square foot production facility with a fleet of 14 cyclotrons close to Atlanta, Georgia, a major US transport hub, for centralised, large-scale copper-64 (Cu-64 or 64Cu) production ahead of anticipated 64Cu-SAR-bisPSMA commercial launch upon successful completion of Clarity’s Phase III registrational trials with this product, AMPLIFY1 and CLARIFY2, and subsequent US Food and Drug Administration (FDA) New Drug Application (NDA) approval.

Theragenics have substantial cyclotron expertise with 40 years of routine radiometal production and considerable experience in production of radioisotopes for medical use. Combined with a sizeable fleet of high-current cyclotrons, this constitutes an opportunity for large-scale copper-64 manufacturing at the site. Theragenics have capacity to produce around 100Ci (3.7 TBq) of copper-64 per day on a single cyclotron, which translates into around 2,000 patient doses per day on each cyclotron at 200 MBq per dose with a 48-hour shelf life. Together with Clarity’s existing copper-64 supply agreements with SpectronRx and Nusano, this agreement with Theragenics further enhances Clarity’s broad network of high-volume copper-64 manufacturers in distinct US geographies. The network is designed to support commercial-scale demand across multiple large oncology indications with secure, seamless and abundant supply of this diagnostic isotope, made possible with the 12.7-hour half-life of copper-64, which is unique in the radiopharmaceutical commercial space.

Mark Pugh, CEO of Theragenics, commented, "We are excited to enter into this Manufacturing Supply Agreement for copper-64 with Clarity. Having a current commercial sales force in prostate cancer, we have a deep insight into this field and have seen the excitement from key opinion leaders around 64Cu-SAR-bisPSMA. This agreement continues our expansion into the contract manufacturing organisation (CMO) isotope market, and we see Clarity as an ideal partner to advance this vision. Clarity is in a unique position with two diagnostic Phase III trials nearing completion, three Fast Track Designations (FTDs) from the US FDA and impressive data generated to date. With our core expertise and experience in producing radiometals for commercial medical purposes at Theragenics, together we can expand access to radiopharmaceuticals and bring a next-generation platform to patients in need of better diagnostics in the US."

Dr Alan Taylor, Executive Chairperson of Clarity Pharmaceuticals, commented, "Clarity is closer than ever to commercialisation of 64Cu-SAR-bisPSMA, with outstanding data recently released from the head-to-head Co-PSMA investigator-initiated trial3 and our announcement on achieving our target number of participants in the Phase III AMPLIFY trial just months since imaging the first patient4.

"The growing body of scientific evidence, along with the FTDs from the FDA are providing great momentum for 64Cu-SAR-bisPSMA. Building out a secure, reliable and abundant supply and manufacturing strategy is now coming into play, ensuring a solid base for our commercial launch and accelerated market expansion, subject to FDA approval. Our team is committed to continue working closely with our vendors, clinicians, participating clinical trial sites, regulatory agencies and supply and manufacturing facilities to get 64Cu-SAR-bisPSMA to patients in need as soon as possible, at scale to meet the future demand.

"The longer half-life of copper-64 (12.7 hours vs. less than 2 hours for the radionuclides currently used in prostate-specific membrane antigen [PSMA] positron emission tomography [PET], i.e. gallium-68 and fluorine-18) translates into a shelf-life of up to 48 hours for 64Cu-SAR-bisPSMA. As such, copper-64 offers greater flexibility for supply and scheduling of patients, overcoming various limitations of the short half-life isotopes currently used in radiodiagnostics. This represents a unique opportunity to implement a multi-tiered service approach comprising of large, local, centralised manufacturing with broad geographic distribution. Importantly, we have the opportunity to avoid the excessive costs, waste and inefficiencies associated with the supply and manufacture of short half-life isotopes. Our goal is to take the industry in a new direction of scalability and profitability while delivering universal access to radiodiagnostics for physicians and the patients they serve.

"Theragenics has decades of experience in the commercial production of radiometals for medical purposes and valuable insight into the prostate cancer field based on their existing brachytherapy business. We look forward to working with them as we prepare to take the next steps in our development."

The Manufacturing Supply Agreement is effective as of 25 March 2026. Cancellation and extension provisions are aligned with industry standard rates.

(Press release, Clarity Pharmaceuticals, MAR 25, 2026, View Source [SID1234663861])

Callio Therapeutics Doses First Patient in Phase I Clinical Trial of Dual-Payload ADC CLIO-8221 in Advanced HER2-Expressing Solid Tumors

On March 24, 2026 Callio Therapeutics, a biotherapeutics company advancing dual-payload antibody-drug conjugates (ADCs) with a targeted, multi-mechanism approach to cancer treatment, reported that the first patient has been dosed in a Phase I clinical trial evaluating CLIO-8221 in patients with advanced HER2-expressing solid tumors. CLIO-8221 is a novel, first-in-class dual-payload ADC targeting HER2, engineered for targeted delivery of two payload classes: a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, to HER2-expressing tumors.

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The Phase I clinical trial (NCT07300943) is ongoing in Australia and the U.S., with Callio Therapeutics having received IND clearance from the U.S. Food and Drug Administration (FDA) this month. The IND is also under review by the China National Medical Products Administration (NMPA), and the trial is expected to expand to multiple sites in China.

"Dosing the first patient in the Phase I trial in Australia and receiving IND clearance from the U.S. FDA are significant steps in our commitment to advancing dual-payload ADCs for patients with cancer," said Piers Ingram, Ph.D., Chief Executive Officer of Callio Therapeutics. "CLIO-8221 is the first program from Callio’s dual-payload ADC pipeline to enter the clinic, achieved in just a year from our launch. We believe this dual-payload ADC approach represents a promising new modality for multi-mechanism targeted cancer treatment."

"CLIO-8221 uses a potent combination of two complementary anti-cancer payloads to address a common mechanism that causes resistance to single-payload ADCs. In preclinical models, CLIO-8221 demonstrated compelling anti-tumor activity, with a single dose leading to tumor regression in both Topo1 inhibitor-insensitive and -refractory models and was significantly more effective than single-payload ADCs," said Jerome Boyd-Kirkup, Ph.D., Chief Scientific Officer of Callio Therapeutics. "Callio is actively developing a pipeline of promising dual-payload ADCs with rationally selected payload combinations. We are excited to move this pipeline into clinical trials in the upcoming months."

"We are committed to improving treatment options for patients and are excited to take this step with CLIO-8221," said Naomi Hunder, M.D., Chief Medical Officer of Callio Therapeutics. "CLIO-8221 represents a major advance in ADC technology, combining the validated cytotoxic payload exatecan with an ATR inhibitor payload. For patients whose cancers have become resistant or do not respond to existing Topo1 inhibitor-based ADCs, this dual-payload approach offers a new potential treatment option. Patients may also benefit from improved safety, as our next-generation linker platform is designed to reduce toxicities, consistent with the broad therapeutic window observed in preclinical studies."

About CLIO-8221

HER2 is a clinically validated target for antibody-drug conjugates (ADCs), with multiple approved therapies demonstrating meaningful benefit across tumor types, however, most patients eventually progress on treatment despite retaining HER2 expression. Mechanistic resistance to cytotoxic payloads has emerged as a key reason for treatment failure. CLIO-8221 is a novel, first-in-class dual-payload ADC targeting HER2, designed to address this challenge.

CLIO-8221 delivers two mechanistically complementary payloads, a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, directly to HER2-expressing tumors. While Topo1 inhibitors have shown strong clinical activity, activation of the DNA damage response following Topo1 inhibitor-induced replication stress represents a potential major driver of resistance. By simultaneously inhibiting Topo1 and blocking the DNA damage response through ATR inhibition, CLIO-8221 is engineered to overcome payload insensitivity and sensitize tumors to Topo1 inhibition. Developed using proprietary linker and ADC platform technologies, CLIO-8221 aims to maximize anti-tumor activity while reducing systemic toxicity, offering the potential for deeper and more durable responses in patients who have progressed on existing HER2-targeted therapies.

(Press release, Callio Therapeutics, MAR 24, 2026, View Source [SID1234663888])