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.

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 topline data from its Phase 2 ASPEN-03 and ASPEN-04 clinical trials (Press release, ALX Oncology, APR 25, 2025, View Source [SID1234652135]). The company’s investigational CD47-blocker evorpacept, when added to Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) with or without chemotherapy, did not meet the primary endpoints in the ASPEN-03 and ASPEN-04 trials of improved objective response rates (ORR) as compared to historical controls of pembrolizumab alone and pembrolizumab with chemotherapy, respectively, as a first-line treatment in patients with advanced head and neck squamous cell carcinoma (HNSCC). The combination of evorpacept and pembrolizumab with or without chemotherapy in ASPEN-03 and ASPEN-04 demonstrated a manageable safety profile and was consistent with what has been previously reported for pembrolizumab and chemotherapy in this setting. Although the company will no longer pursue evorpacept in combination with pembrolizumab in HNSCC, multiple clinical trials of evorpacept in combination with anti-cancer antibodies will continue based on established proof-of-concept.

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Evorpacept blocks the ‘don’t eat me’ signal transmitted by CD47 on the surface of cancer cells that these cells use to evade detection by the immune system. As its primary mechanism of action, evorpacept is uniquely designed to stimulate macrophages to selectively attack cancer cells and not healthy cells, when combined with active anti-cancer antibodies. This mechanism has translated into durable clinical responses and a well-tolerated safety profile in HER2-positive gastric and HER2-positive breast cancer clinical trials. To further explore the benefit in this setting, evorpacept is currently being evaluated in combination with various anti-cancer antibodies in colorectal cancer, breast cancer, non-Hodgkin lymphoma and multiple myeloma.

In the ASPEN-03 and ASPEN-04 clinical trials, evorpacept was combined with pembrolizumab with or without chemotherapy to investigate a second and distinct mechanism of action. This discrete approach explored the concept that evorpacept may enhance T-cell priming by activating dendritic cells and stimulating the adaptive immune system. The trial outcomes were not sufficiently supportive of advancing evorpacept in combination with pembrolizumab in HNSCC into a registrational trial.

"While there were encouraging trends in ASPEN-03 in ORR versus the historical and internal control, we’ve decided not to pursue evorpacept and pembrolizumab in head and neck cancer in light of our prioritization of the more established anti-cancer antibody combination program based on multiple positive studies," said Alan Sandler, M.D., Chief Medical Officer at ALX Oncology. "We are disappointed that these studies did not meet their primary endpoints, most importantly for the patients for whom current standard-of-care treatment approaches fall short, and we thank all who participated in the trials."

"Moving forward, we are continuing to rapidly advance our clinical program combining evorpacept with anti-cancer antibodies supported by robust clinical data across trials in multiple tumor types. Evorpacept has demonstrated response rates and durability beyond what is expected from standard of care across several studies when combined with HERCEPTIN, zanidatamab and RITUXAN," said Jason Lettmann, Chief Executive Officer at ALX Oncology. "Based on the positive data and strong mechanistic rationale, we maintain our confidence in the evorpacept clinical development program and intend to deliver on that promise with additional clinical data in breast cancer and colorectal cancer in the near-term. With evorpacept and ALX2004, our novel EGFR-targeted antibody-drug conjugate, we continue our commitment to bringing forth meaningful therapies for patients living with cancer."

Detailed findings from the ASPEN-03 and ASPEN-04 trials will be submitted to a future medical meeting.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ASPEN-03 and ASPEN-04 Clinical Trials
ASPEN-03 and ASPEN-04 are randomized, multi-center, international Phase 2 trials evaluating evorpacept, ALX Oncology’s investigational CD47-blocking therapeutic that uniquely combines a high-affinity CD47-binding domain with an inactivated proprietary Fc domain, in patients with metastatic or unresectable, recurrent HNSCC who have not yet been treated for their advanced disease. The ASPEN-03 trial (NCT04675294) is evaluating evorpacept in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) against pembrolizumab alone for the treatment of patients whose HNSCC is PD-L1 positive. The ASPEN-04 trial (NCT04675333) is evaluating evorpacept in combination with pembrolizumab and chemotherapy against pembrolizumab and chemotherapy alone in patients with HNSCC, regardless of PD-L1 status. Patient characteristics in the trials (N=346) were generally well-balanced across arms. The primary endpoints for the ASPEN-03 and ASPEN-04 trials is ORR compared to historical control. Key secondary endpoints for both trials are safety, duration of response (DOR), progression-free survival (PFS) and overall survival (OS).

About Head and Neck Squamous Cell Carcinoma (HNSCC)
HNSCC is a serious and life-threatening disease that originates in the squamous cells lining the mucosal surfaces of the head and neck, including the mouth, throat, voice box, sinuses and nasal cavity. HNSCC is the seventh most common cancer worldwide and the incidence of HNSCC is expected to increase 30% by 2030. Despite current standard-of-care therapies and recent advancements in diagnosis and treatment, people with HNSCC face a poor prognosis, particularly when diagnosed at advanced stages. Further, the survival rate for HNSCC has only modestly improved in recent years, even with the availability of new treatment modalities, underscoring a need for improved therapeutics.

About Evorpacept
ALX Oncology’s lead therapeutic candidate, evorpacept, is a highly differentiated potential best- and first-in-class CD47 checkpoint inhibitor and one of the most advanced checkpoint inhibitors to target and activate the innate immune system. Evorpacept was intentionally designed to maximize the clinical potential of blocking CD47, while reducing the toxicities associated with previous approaches to CD47 blockade. In clinical studies across a wide spectrum of tumor types in more than 700 patients to date, evorpacept has demonstrated potential to enhance the therapeutic activity of many of the most important cancer therapies available today, contributing an additional, differentiated immuno-oncology mechanism. Based on this potential, ALX Oncology is advancing a robust clinical program evaluating evorpacept in a wide range of cancer indications, prioritizing its combination with anti-cancer antibodies in breast, gastric and colon cancers. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to evorpacept for the second-line treatment of patients with HER2-positive gastric or GEJ carcinoma. Additionally, both the FDA and European Commission have granted Orphan Drug Designation for this indication.