On April 25, 2025 CatalYm reported the presentation of the first preclinical data demonstrating that the company’s clinical-stage antibody visugromab can improve the anti-tumor activity of antibody-drug conjugates (ADCs). The data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place in Chicago, IL, April 25-30, 2025 (Press release, Catalym, APR 25, 2025, View Source [SID1234652140]). The poster will highlight the potential of targeting Growth Differentiation Factor 15 (GDF-15) to enhance the activity and overcome resistance to ADC therapies, which are increasingly used as frontline treatments in several solid tumor indications. The full abstract is available on the AACR (Free AACR Whitepaper) Annual Meeting website.

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The study showed that several clinically validated ADCs, including topoisomerase I and microtubule inhibitor-based regimens, consistently triggered GDF-15 expression, suggesting a potential resistance mechanism to ADC therapy. Across in vitro and in vivo models of multiple solid tumor types, ADC treatment induced GDF-15 release from tumor cells, leading to elevated serum levels and reduced ADC efficacy. Combining ADC treatment with GDF-15 neutralization improved anti-tumor responses, resulting in reduced tumor growth and enhanced infiltration and activation of T cells and myeloid cells in the tumor microenvironment.

"We are building a broader understanding of GDF-15 as a key resistance mechanism activated by targeted approaches like ADCs as well as the leading immunotherapies like PD-1 inhibitors," said Christine Schuberth-Wagner, PhD, Chief Scientific Officer at CatalYm. "By blocking GDF-15, visugromab restores anti-tumor immune activity and enhances treatment efficacy, underscoring its potential as a versatile combination partner across a broad spectrum of cancer therapies beyond immunotherapies."

"ADCs continue to demonstrate potent and specific therapeutic impact, nevertheless resistance is a significant challenge for long-term patient benefit. In addition to our Phase 2 clinical development program, CatalYm will continue to investigate how our GDF-15 neutralizing antibody visugromab can create a novel path to address cancer resistance effectively," added Scott Clarke, Chief Executive Officer at CatalYm.

The preclinical findings build on clinical evidence from the GDFATHER-1/2a trial (GDF-15 Antibody-mediaTed Human Effector T Cell Relocation Phase 1/2a Trial; NCT04725474), that was recently published in Nature. The data show that visugromab induces deep and durable responses in patients with relapsed or refractory solid tumors who had progressed on prior anti-PD-1/PD-L1 therapies. In addition to restoring anti-tumor immune responses, visugromab also demonstrated the potential to mitigate cancer-associated cachexia. CatalYm is currently conducting a broad, global Phase 2b clinical development program for visugromab, evaluating its effectiveness in earlier treatment lines of non-squamous non-small-cell lung cancer and hepatocellular carcinoma, as well as neoadjuvant treatment in urothelial cancer in combination with standard of care.

Poster details

Session title: "PO.IM01.03 – Antibodies and Antibody-Drug Conjugates"

Abstract title: "GDF-15 neutralization enhances the therapeutic activity of antibody-drug conjugates"

Abstract number: 4777/13

Location: Section 36

Date and time: April 29, 2025, 9:00 AM – 12 PM CT/ 4:00 PM – 7:00 PM CEST

About Visugromab
Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation and induction of interferon-γ.

On April 25, 2025 Baylink Biosciences reported data from its Antibody Drug Conjugate portfolio at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL (Press release, Baylink Biosciences, APR 25, 2025, View Source [SID1234652139]). The data presented for BLB-101, an antibody drug conjugate targeting Claudin 6 and 9 delivering exatecan, represents a potential best-in-class profile. In addition, Baylink presented data demonstrating its novel next-generation ADC linker technology is able to overcome key challenges in ADC development.

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"The data presented today at AACR (Free AACR Whitepaper) provides strong evidence of BLB-101’s best-in-class profile. We believe BLB-101 is the only ADC with dual targeting of Claudin 6 and 9, with the ability to impact heterogenous tumors and benefit more patients with ovarian and other CLDN6/9+ tumor types. We plan to file an IND for this exciting candidate in 2026," said Alice Chen, PhD, Chief Scientific Officer and Founder of Baylink. "In addition, our scientists presented data at the meeting showcasing our innovative linker technology which has been designed to overcome a number of key challenges in the ADC field. In particular, our linker technology enables the delivery of new payload classes such as degraders and the delivery of two modalities in a dual payload ADC format, approaches that we believe will help to overcome resistance to chemotherapy, a significant unmet need."

Presentation Highlights

Preclinical evaluation of BLB-101, a topoisomerase-inhibitor-based anti-CLDN6/9 antibody-drug conjugate featuring a proprietary hydrophilic linker

Poster number：1578

Session Date and Time: April 28, 2025, 9:00 AM – 12:00 PM

BLB-101 is an antibody drug conjugate designed to target Claudin 6/9 and deliver the topoisomerase 1 inhibitor, exatecan in a highly efficient manner with a drug to antibody ratio of 8. Claudin 6 (CLDN6) is a tight junction protein that is highly expressed in various human cancers, including ovarian cancer, endometrial cancer, and non-small cell lung cancer (NSCLC), but is absent in normal adult tissues. Claudin 9 (CLDN9), which shares high homology with CLDN6, exhibits a similar expression pattern—being nearly undetectable in normal tissues but upregulated in ovarian and endometrial cancers. The compelling preclinical activity profile supports BLB-101 development for Claudin 6/9 positive tumors. An investigational new drug submission is planned for 2026.

Key Results:

We successfully identified a high-affinity antibody, 2D5S, that specifically binds to CLDN6 and CLDN9 while avoiding interaction with other Claudin family members. BLB-101 is an antibody-drug conjugate (ADC) candidate that incorporates 2D5S (CLDN6/9 Ab) and the topoisomerase I inhibitor, exatecan as payload, along with our proprietary hydrophilic linker, BL001. BLB-101 demonstrates excellent biological activity, favorable in vivo pharmacokinetics (PK), and excellent developability. It exhibits strong cytotoxic effects across multiple antigen-positive cancer cell lines. In xenograft models expressing CLDN6 or CLDN9, BLB-101 achieved tumor elimination at low doses. Additionally, BLB-101 was well tolerated in non-human primates. Collectively, these findings provide strong support for the continued clinical development of BLB-101.

• 2D5S Ab binds with high affinity to CLDN6 and CLDN9 while sparing other claudin

family members.

• 2D5S demonstrates stronger internalization compared to a benchmark antibody.

• BLB-101 is a DAR8 ADC featuring a topoisomerase 1-inhibitor-based payload with a

proprietary hydrophilic linker, BL001.

• BLB-101 exhibits strong in vitro cytotoxic and bystander killing effects.

• In xenograft models, BLB-101 treatment resulted in robust tumor elimination at dose as low as 1 mg/kg.

• BLB-101 demonstrated outstanding plasma stability and favorable PK in cynomolgus monkey.

• BLB-101 is well-tolerated in cynomolgus monkeys up to 40 mg/kg, suggesting an

extended therapeutic window.

A linker platform for antibody drug conjugates (ADCs): expanding the therapeutic window

Poster number：7463

Session Date and Time: April 30, 2025, 9:00 AM – 12:00 PM

Key Results:

Our novel linker designs offer significant advantages, with features that could expand the therapeutic window of current ADCs by improving their hydrophilicity and stability, and reducing off–target effects while maintaining efficacy. The linkers have been applied to several projects with the frontrunner project scheduled to enter a phase 1clinical trial in 2026. We are also expanding the utility of this class of linkers to enable innovative design of dual–payload–ADC and Degrader–Antibody–Conjugates.

• Baylink’s proprietary linker BL001 improves hydrophilicity and stability of ADC

• BL001 linker reduced non-specific uptake of ADC into non-cancerous cells via macropinocytosis

• BL001 linker utilized in a trastuzumab exatecan ADC showed superior antitumor effect to GGFG based ADC delivering Dxd.

• BL001 linker utilized in BLB-101 candidate showed excellent PK and tolerability in cynomolgus monkeys, predicting an enhanced therapeutic index.

Copies of the poster presentations will be available on the Baylink Biosciences website at www.Baylinkbio.com/blog following the AACR (Free AACR Whitepaper) meeting.

On April 25, 2025 Azitra, Inc. (NYSE American: AZTR), a clinical stage biopharmaceutical company focused on developing innovative therapies for precision dermatology, reported that an abstract detailing the Phase 1/2 clinical trial of ATR04-484 in EGFR inhibitor ("EGFRi")-associated rash has been accepted for presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held May 30-June 3, 2025 in Chicago (Press release, Azitra, APR 25, 2025, View Source [SID1234652138]).

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"We look forward to presenting an update on the ATR-04 program at ASCO (Free ASCO Whitepaper) as we plan to dose the first patient in the first half of 2025," said Francisco Salva, CEO of Azitra. "ASCO is widely regarded as the most prestigious cancer research conference in the world, and we are eager to educate leaders in the oncology community on the potential of ATR04-484 to treat the unique dermatologic toxicities that often accompany EGFRi treatments, which can hamper treatment efforts and cause significant physical and psychological discomfort for patients."

ATR04-484 is a live biotherapeutic product candidate including an isolated, naturally derived Staphylococcus epidermidis strain that was engineered to be safe by deleting an antibiotic resistance gene and engineering auxotrophy to control the growth of ATR04-484. ATR04-484 is in development for EGFRi-associated skin rash, which is associated with the suppression of skin immunity by EGFR inhibitors and subsequent inflammation, often accompanied by elevated levels of IL-36γ and S. aureus. Azitra has received Fast Track designation from the FDA for EGFRi associated rash and has initiated a Phase 1/2 clinical study in patients with EGFRi rash with the first patient expected to be dosed in the first half of 2025.

EGFR inhibitors are a class of cancer drugs that target and block the activity of the EGFR protein, which plays a crucial role in cell growth and survival. They are primarily used to treat certain types of cancer, including non-small cell lung cancer (NSCLC) and colorectal cancer.

The full ASCO (Free ASCO Whitepaper) abstracts will be available on May 22, 2025, after 5 p.m. ET. Abstract titles are available at: View Source

On April 25, 2025 Astellas reported financial results for FY2024 (Press release, Astellas, APR 25, 2025, View Source [SID1234652137]).

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On April 25, 2025 ALX Oncology Holdings Inc., ("ALX Oncology" or the "Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, reported encouraging data from an ongoing Phase 1/2 investigator-sponsored trial (IST) of the company’s lead clinical candidate, evorpacept, in combination with standard-of-care rituximab and lenalidomide (R2) in patients with indolent and aggressive relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) (Press release, ALX Oncology, APR 25, 2025, View Source [SID1234652136]). Final results from the Phase 1 portion of the trial will be presented Tuesday, April 29, during a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR) Annual Meeting 2025 in Chicago, Illinois.

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"In patients with indolent B-NHL, increases in certain pro-tumoral macrophages can promote resistance to important frontline standard-of-care treatments, including R2," said Paolo Strati, M.D., the trial’s lead investigator and Associate Professor of Lymphoma-Myeloma at The University of Texas MD Anderson Cancer Center. "Evorpacept is uniquely designed to activate the innate immune system and engage macrophages to enhance the therapeutic benefits of and deepen responses to anti-cancer antibodies such as rituximab. This trial suggests evorpacept has a synergistic effect with R2 that may help improve outcomes and overcome resistance to R2 in this patient population."

The clinical trial conducted by Dr. Strati and colleagues at MD Anderson enrolled a total of 20 patients with indolent (n=18) and aggressive (n=2) R/R B-NHL; all 20 had previously received an anti-CD20 monoclonal antibody (rituximab), 72% had received prior chemoimmunotherapy and 80% had progressed within 24 months from frontline therapy. Patients with indolent NHL had received at least one prior line of systemic therapy. Investigators administered the CD47-blocker evorpacept at two dose levels: 30 mg/kg Q2W (n=3) or 60 mg/kg Q4W (n=17) in combination with standard R2 treatment. The regimen was well- tolerated, and there were no dose-limiting toxicities.

After a median follow-up of 28 months (95% CI, 18-28 months) the two-year progression-free survival (PFS) rate was 69% and two-year overall survival (OS) rate was 84%. Sixteen patients (80%) achieved complete responses and the best overall response rate (ORR) was 90%. As previously reported at the AACR (Free AACR Whitepaper) 2024 Annual Meeting, the CR rate among the 18 patients with iNHL was 83%. This complete response rate achieved by evorpacept + R2 in this trial compares favorably to the 34% historical CR rate for R2 alone. During treatment, a significant increase in T cells and anti-tumoral macrophages was observed.

"The final results from this Phase 1 study reinforce evorpacept’s potential to meaningfully deepen and enhance responses to many of the most important cancer therapies available today, including anti-cancer antibodies such as rituximab, and to thereby help address significant, unmet needs in cancer treatment," said Jason Lettmann, Chief Executive Officer of ALX Oncology. "We look forward to the continued evaluation of evorpacept in patients with previously untreated and high tumor-burden indolent NHL in the Phase 2 portion of this study."

The Phase 2 portion of this IST in patients with previously untreated iNHL is ongoing and has completed enrollment.

Details of the poster to be presented at AACR (Free AACR Whitepaper) 2025 are as follows:

Title: Final results of a phase I trial of evorpacept (ALX148), lenalidomide, and rituximab for patients with B-cell non-Hodgkin lymphoma
Presenter: Paolo Strati, M.D., Associate Professor of Lymphoma-Myeloma, The University of Texas MD Anderson Cancer Center
Session Title: Late-Breaking Research: Clinical Research 3
Date/Time: Tuesday, April 29, 2025, from 2:00 p.m. – 5:00 p.m. CT
Location: McCormick Place Convention Center, Poster Section 53
Poster Board Number: 13
Published Abstract Number: LB369

A copy of the AACR (Free AACR Whitepaper) 2025 IST presentation will be available in the "Publications" section of the ALX Oncology website following the presentation.