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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

On April 25, 2025 AbbVie (NYSE:ABBV) reported financial results for the first quarter ended March 31, 2025 (Press release, AbbVie, APR 25, 2025, View Source [SID1234652133]).

"AbbVie’s first-quarter results were well ahead of our expectations and reflect an excellent start to the year," said Robert A. Michael, chief executive officer, AbbVie. "The fundamentals of our business are strong and we continue to bolster our outlook with pipeline advancements and strategic investments. Based on the progress we are making, AbbVie is well positioned for the long term."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

First-Quarter Results

•Worldwide net revenues were $13.343 billion, an increase of 8.4 percent on a reported basis, or 9.8 percent on an operational basis.

•Global net revenues from the immunology portfolio were $6.264 billion, an increase of 16.6 percent on a reported basis, or 18.1 percent on an operational basis.
◦Global Skyrizi net revenues were $3.425 billion, an increase of 70.5 percent on a reported basis, or 72.0 percent on an operational basis.
◦Global Rinvoq net revenues were $1.718 billion, an increase of 57.2 percent on a reported basis, or 59.7 percent on an operational basis.
◦Global Humira net revenues were $1.121 billion, a decrease of 50.6 percent on a reported basis, or 49.5 percent on an operational basis.

•Global net revenues from the neuroscience portfolio were $2.282 billion, an increase of 16.1 percent on a reported basis, or 17.0 percent on an operational basis.
◦Global Vraylar net revenues were $765 million, an increase of 10.3 percent.
◦Global Botox Therapeutic net revenues were $866 million, an increase of 15.8 percent on a reported basis, or 17.0 percent on an operational basis.
◦Global Ubrelvy net revenues were $240 million, an increase of 17.8 percent on a reported basis, or 18.0 percent on an operational basis.
◦Global Qulipta net revenues were $193 million, an increase of 47.6 percent on a reported basis, or 48.3 percent on an operational basis.

•Global net revenues from the oncology portfolio were $1.633 billion, an increase of 5.8 percent on a reported basis, or 7.5 percent on an operational basis.
◦Global Imbruvica net revenues were $738 million, a decrease of 11.9 percent.
◦Global Venclexta net revenues were $665 million, an increase of 8.3 percent on a reported basis, or 12.3 percent on an operational basis.
◦Global Elahere net revenues were $179 million.

•Global net revenues from the aesthetics portfolio were $1.102 billion, a decrease of 11.7 percent on a reported basis, or 10.2 percent on an operational basis.
◦Global Botox Cosmetic net revenues were $556 million, a decrease of 12.3 percent on a reported basis, or 10.7 percent on an operational basis.
◦Global Juvederm net revenues were $231 million, a decrease of 22.2 percent on a reported basis, or 20.0 percent on an operational basis.

•On a GAAP basis, gross margin in the first quarter was 70.0 percent. The adjusted gross margin was 84.1 percent.

•On a GAAP basis, selling, general and administrative (SG&A) expense was 24.7 percent of net revenues. The adjusted SG&A expense was 24.6 percent of net revenues.

•On a GAAP basis, research and development (R&D) expense was 15.5 percent of net revenues. The adjusted R&D expense was 15.4 percent of net revenues.

•Acquired IPR&D and milestones expense was 1.9 percent of net revenues.

•On a GAAP basis, operating margin in the first quarter was 28.0 percent. The adjusted operating margin was 42.3 percent.

•Net interest expense was $627 million.

•On a GAAP basis, the tax rate in the quarter was 22.4 percent. The adjusted tax rate was 14.2 percent.

•Diluted EPS in the first quarter was $0.72 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $2.46. These results include an unfavorable impact of $0.13 per share related to acquired IPR&D and milestones expense.

Recent Events

•AbbVie announced that its board of directors unanimously elected chief executive officer (CEO) Robert A. Michael to assume the additional position of chairman of the board of directors, effective July 1, 2025. He will succeed Richard A. Gonzalez, who formerly served as AbbVie’s CEO and has been chairman since the Company’s formation in 2013.

•AbbVie announced that the European Commission (EC) granted marketing authorization to Rinvoq (upadacitinib) for the treatment of giant cell arteritis (GCA) in adult patients. The approval was supported by data from the pivotal Phase 3 SELECT-GCA trial which demonstrated that Rinvoq achieved the primary endpoint of sustained remission and key secondary endpoints, including reduction in disease flares, lower cumulative steroid exposure and complete remission. This authorization marks the eighth approved indication for Rinvoq in the European Union (EU).

•At the Society of Gynecologic Oncology (SGO) Annual Meeting, AbbVie announced final data analysis from the Phase 3 MIRASOL trial evaluating the efficacy and safety of Elahere (mirvetuximab soravtansine-gynx) in women with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer (PROC) compared to chemotherapy. At 30.5 months median follow-up, treatment with Elahere continued to show significant improvements in progression-free survival (PFS) and overall survival (OS) compared to investigator’s choice (IC) chemotherapy.

•AbbVie and Xilio Therapeutics, a clinical-stage biotechnology company, announced a collaboration and option-to-license agreement that will combine AbbVie’s oncology expertise with Xilio’s proprietary tumor-activation technology to develop novel immunotherapies, including masked T-cell engagers, for people living with cancer.

•AbbVie announced that it submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for approval of trenibotulinumtoxinE (BoNT/E) for the treatment of moderate to severe glabellar lines. TrenibotulinumtoxinE is a first-in-class botulinum neurotoxin serotype E characterized by a rapid onset of action as early as 8 hours after administration and short duration of effect of 2-3 weeks. If approved, trenibotulinumtoxinE will be the first neurotoxin of its kind available to patients.

•Allergan Aesthetics announced that the Allergan Medical Institute (AMI) will open three new state-of-the-art training centers in the U.S., expanding access to high-quality, tailored training for licensed aesthetics providers. The first training center is scheduled to open in Irvine, CA, with additional locations to follow in Atlanta, GA and Austin, TX.

•AbbVie and Gubra announced a license agreement to develop GUB014295 (ABBV-295), a potential best-in-class, long-acting amylin analog for the treatment of obesity. This partnership marks AbbVie’s entrance into the obesity field and under the terms of the agreement, AbbVie will lead development and commercialization of GUB014295 globally. Prior to the close of the agreement, Gubra announced positive interim results from Part A of a Phase 1 multiple ascending dose (MAD) study, which showed that GUB014295 was well tolerated with body weight loss that was sustained in a manner consistent with data from a previously announced single ascending dose (SAD) study.

•AbbVie announced that the FDA approved Emblaveo (aztreonam and avibactam), as the first monobactam/β-lactamase inhibitor combination antibiotic therapy to treat complicated intra-abdominal infections, including those caused by Gram-negative bacteria. The approval of Emblaveo was supported by prior findings regarding the efficacy and safety of aztreonam for the treatment of complicated intra-abdominal infections as well as clinical trial results from the Phase 3 REVISIT study, which evaluated the efficacy, safety, and tolerability of Emblaveo for the treatment of serious infections due to Gram-negative bacteria.

Full-Year 2025 Outlook

AbbVie is raising its adjusted diluted EPS guidance for the full year 2025 from $11.99 – $12.19 to $12.09 – $12.29, which includes an unfavorable impact of $0.13 per share related to acquired IPR&D and milestones expense incurred year-to-date through the first quarter 2025. The company’s 2025 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred beyond the first quarter of 2025, as both cannot be reliably forecasted. This guidance does not reflect the acquired IPR&D and milestones impact related to AbbVie and Gubra’s licensing agreement to develop GUB014295, as that transaction closed after the first quarter of 2025. Additionally, this guidance is based on the existing trade environment and does not reflect any trade policy shifts, including pharmaceutical sector tariffs, that could impact AbbVie’s business.

On April 24, 2025 Sanofi reported its first quarter 2025 financial results (Press release, Sanofi, APR 24, 2025, View Source [SID1234654329]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On April 24, 2025 Orion reported interim financial report (Presentation, Orion, APR 24, 2025, View Source [SID1234654277]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!