Press Release

Apexigen Announces New Phase 2 Clinical Data on CD40 Antibody Sotigalimab at the SITC 2021 Annual Meeting

  • Prolonged tumor response and prolonged disease control were observed in anti-PD(L)-1 refractory melanoma patients treated with sotigalimab in combination with nivolumab

  • Biomarker data in metastatic pancreatic cancer patients treated with sotigalimab and chemotherapy demonstrated a unique immune response consistent with sotigalimab's distinct mechanism of action

  • Sotigalimab in combination with radiation therapy was well tolerated and led to the activation of anti-cancer immune cells in rectal cancer patients

SAN CARLOS, CA, November 12, 2021 – Apexigen, Inc., a clinical-stage biopharmaceutical company focused on discovering and developing a new generation of antibody therapeutics for oncology, today announced new clinical data on sotigalimab in three poster presentations at the Society for Immunotherapy of Cancer’s (SITC) 36th Annual Meeting, being held both virtually and in Washington, D.C., November 10-14, 2021. Sotigalimab, Apexigen’s lead immuno-oncology (I-O) therapeutic, is a potentially first-in-class and best-in-class CD40 agonist, with unique epitope specificity and Fc receptor engagement for optimal therapeutic effect and tolerability.

“The exciting new data presented at SITC further validate our broad development strategy by showing that combining sotigalimab with other anti-cancer therapies may provide superior clinical benefits across multiple indications,” said Frank Hsu, M.D., Chief Medical Officer of Apexigen. “To maximize the full therapeutic potential of sotigalimab and overcome outstanding challenges in oncology, we are currently conducting several Phase 2 trials with pioneers and leading oncology research organizations. We look forward to building upon our foundation of compelling proof-of-concept data by leveraging important learnings from ongoing trials and advancing our rapidly progressing clinical program.”

The posters will be available on-demand through the SITC conference portal starting Friday, November 12, 2021, at 7:00 a.m. ET. Additional details on the posters are provided below.

Sotigalimab for Anti-PD-(L)1 Refractory Melanoma

Poster (#389), titled “Phase II of CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy,” is being presented by Harriet Kluger, M.D., Professor of Medical Oncology at Yale School of Medicine. The abstract was selected by members of the SITC Communications Committee to be presented at the SITC 2021 Annual Meeting Press Conference, which is a virtual session showcasing selected abstracts.

Presentation Highlights

Key Takeaway: The combination of sotigalimab and the PD-1 inhibitor nivolumab resulted in treatment benefits (prolonged tumor response or prolonged disease control) in poorly responsive anti-PD-(L)1 refractory melanoma patients with an overall favorable safety and tolerability profile.

  • Objective response rate (ORR) was 15.2% and stable disease (SD) rate was 33.3% in evaluable patients (n=33).
  • Durable responses up to 25+ months were observed, and at completion of therapy and study follow-up, 4/5 patients remained in partial response (PR) without further systemic therapy. SD was observed up to 14.8 months.
  • Sotigalimab in combination with nivolumab was well tolerated. Adverse events (AEs) considered related to sotigalimab or nivolumab or both did occur in the majority of patients but were predominantly grade 1 or 2 and transient. There was a low incidence of reported infusion reactions and no cytokine release syndrome. Serious adverse events (SAEs) were reported in 15.8% of patients, but none were considered related to either study agent. Immune related AEs occurred infrequently and not more than expected with nivolumab alone.

“While a small subset of patients with refractory metastatic melanoma may exhibit delayed tumor shrinkage after continued anti-PD-1 therapy, most will not, and effective treatments for this population represent a critical unmet need,” said Dr. Kluger. “We are encouraged by the results showing that the novel combination of nivolumab and sotigalimab led to prolonged tumor response or prolonged disease control with an overall favorable safety and tolerability profile. These exciting data speak to the promise of sotigalimab-based combinations and their potential to pave the way for novel I-O strategies that can provide meaningful benefits for patients with anti-PD1/PD-L1 refractory melanoma.”

Sotigalimab for First-Line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)

Poster (#343), titled “Multi-omic Multi-Parameter Circulating Biomarker Analysis in Chemoimmunotherapy Combinations Identifies Unique Immune Activation Signatures in the Pancreatic Cancer Setting,” is being presented by Deena Maurer, Ph.D., Translational Scientist at the Parker Institute for Cancer Immunotherapy.

Presentation Highlights

Key takeaway: Both nivolumab in combination with chemotherapy and sotigalimab in combination with chemotherapy elicit unique immune responses that are consistent with their distinct mechanisms of action. Multi-omic, minimally invasive biomarker approaches in mPDAC can identify clear mechanisms that reflect pharmacodynamic effects.

  • Patients receiving sotigalimab in combination chemotherapy demonstrated:
    • Increases in KI67+ T cells relative to baseline
    • Increases in soluble proteins and chemokines associated with dendritic cell maturation
    • IL-15 induction at cycle 3 day 1, which was unique to sotigalimab-chemotherapy treatment and may be produced by monocytes or macrophages. This can stimulate CD8 T and NK cells
    • Increases in chemokines and soluble proteins associated with helper responses and innate immunity. 

Pancreatic cancer is currently the third deadliest cancer in the nation and identifying clinically meaningful therapeutic options for these patients remains a critical hurdle in oncology drug development. CD40 agonists are known to enhance dendritic cell function through increased surface expression of major histocompatibility complex molecules and the production of pro-inflammatory cytokines. The analyses in this study showed an increase in proteins associated with activation of myeloid dendritic cells in patients treated with sotigalimab and chemo, which further underscores the on-mechanism and differentiated activity consistent with the distinct mechanism of action.

“These findings suggest that these immunotherapies are having their intended effect. Future research will focus on how best to understand any possible connection between these mechanisms and patient response, as well as evaluating these minimally invasive biomarkers for their potential to identify PDAC patients that may benefit from CD40 treatment with chemotherapy,” said Dr. Maurer.

Sotigalimab for Rectal Cancer

Poster (#411), titled “INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer to Elucidate Local and Systemic Therapeutic Responses,” is being presented by Todd Aguilera, M.D., Ph.D., Assistant Professor of Radiation Oncology at UT Southwestern Medical Center, who also consults for Apexigen.

Presentation Highlights

Key takeaway: Sotigalimab in combination with radiation therapy (RT) has the potential to modulate the tumor microenvironment and improve clinical response. These emerging data highlight the importance of evaluating RT with IO agents and the requirement for further study across different tumor types.

  • Responses in the tumor microenvironment (TME): Single-cell RNA sequencing was performed in a patient pre and post sotigalimab and RT. Post treatment analysis revealed the emergence of dendritic cells (DCs) and CD8 T cells.
  • There were no observed DCs, CD4-Th1, or CD8-IFN+/GZMB+ in the TME before treatment. However, after sotigalimab and RT there was an increase of each cell type and DCs were the dominant cell expressing CD40. Transcriptomic changes were observed across many cell subtypes, suggestive of an induction of immune response, increased tumor cell death, and expression of multiple immune checkpoints after sotigalimab.
  • Treatment with sotigalimab and RT has been well tolerated across all patients.

About the Phase 2 Clinical Trials

The Phase 2 dose-expansion trial in patients with metastatic melanoma who had progressed when previously treated with anti-PD-(L)1 therapy, were treated with sotigalimab 0.3mg/kg combined with nivolumab 360mg every three weeks. The primary endpoints were safety and overall response rate (ORR) measured by RECIST 1.1 criteria. For additional information on this trial see clinicaltrials.gov (NCT03123783).

The Phase 2 multicenter trial patients with previously untreated metastatic pancreatic ductal adenocarcinoma received nivolumab or sotigalimab in combination with standard of care gemcitabine/nab-paclitaxel. Orthogonal minimally invasive biomarker technologies were used to investigate immune activation and pharmacodynamic activity. For additional information on this trial see clinicaltrials.gov (NCT03214250).

The Phase 2 INNATE trial in patients with rectal cancer, is a multi-center, randomization clinical trial that adds sotigalimab to short course radiation treatment and subsequent FOLFOX chemotherapy prior to deļ¬nitive surgery. The trial is planned to enroll 58 patients with stage 3 and high-risk stage 2 rectal cancer with no contraindications for immunotherapy or radiation. The primary endpoint is pathologic complete response. For additional information on this trial see clinicaltrials.gov (NCT04130854).

About Sotigalimab

Sotigalimab is a novel, humanized monoclonal antibody that stimulates the anti-tumor immune response. Sotigalimab targets CD40, a co-stimulatory receptor that is essential for activating both innate and adaptive immune systems. Binding of sotigalimab to CD40 on antigen presenting cells (i.e., dendritic cells, monocytes and B cells) initiates a multi-faceted immune response bringing multiple components of the immune system (e.g., T cells, macrophages) to work in concert against cancer. Sotigalimab is currently in Phase 2 clinical development for the treatment of cancers such as esophageal and gastroesophageal junction, rectal and ovarian cancers, melanoma and sarcoma in various combinations with immunotherapy, chemotherapy, radiation therapy or a cancer vaccine. Additional information on clinical trials for sotigalimab can be found at www.clinicaltrials.gov.

About Apexigen

Apexigen is a clinical-stage biopharmaceutical company focused on discovering and developing a new generation of antibody therapeutics for oncology, with an emphasis on new immuno-oncology agents that may harness the patient’s immune system to combat and eradicate cancer. Sotigalimab and Apexigen’s other programs were discovered using Apexigen’s proprietary APXiMAB™ discovery platform. This platform has enabled Apexigen and its collaboration partners to discover and develop high-quality therapeutic antibodies against a variety of molecular targets, including targets that are difficult to drug with conventional antibody technologies. Seven product or product candidates discovered using APXiMAB are currently commercially available or in clinical development, either internally by Apexigen or by its licensees. For more information, please visit www.apexigen.com.

Investor Contact:

Bruce Mackle
LifeSci Advisors
+1-646-889-1200
bmackle@lifesciadvisors.com

Apexigen Contact:

Mark Nevins
Sr. Vice President, Business Development
Apexigen, Inc.
+1-650-931-6236
mnevins@apexigen.com