Alligator Bioscience

• Early Data Indicate Clinical Activity in Patients with Multiple Solid Tumor Types
• Prolonged stable disease lasting >11 months demonstrated in Breast Cancer Patient
• Favorable Pharmacokinetics, Safety and Tolerability Observed
• Data Presented at the European Society of Medical Oncology on September 14, 2024

Lund, Sweden and Seattle, Washington, September 16, 2024 – Alligator Bioscience AB ("Alligator") (Nasdaq Stockholm: ATORX) and Aptevo
Therapeutics ("Aptevo") (Nasdaq: APVO) today announced positive interim data from the dose escalation phase of their Phase 1 trial evaluating ALG.APV-527 for the treatment of solid tumors likely to express the tumor antigen 5T4. The results, which include clinical activity, safety, tolerability outcomes, pharmacokinetics and pharmacodynamics were presented in a poster session on Saturday, September 14, 2024, at the European Society for Medical Oncology (ESMO) Annual Congress in Barcelona, Spain.

ALG.APV-527 is a first-in-class bispecific antibody that targets 4-1BB and the tumor antigen 5T4. The compound is being evaluated in a multi-center, dose escalation trial that has 18 patients included in the safety analysis. These patients received multiple prior rounds of therapy for the treatment of solid tumor types. The trial is approaching full enrollment and interim results include:

Clinical Activity/Efficacy

• Nine of 15 efficacy evaluable patients (60%) have a best overall response to date of stable disease (SD)
  • The longest SD duration was in a breast cancer patient who entered the study with progressive disease, achieved stable disease and remained on study for >11 months. This patient successfully transitioned to a higher dose level twice
  • One colon cancer patient with sustained SD remains on study for more than four months

Safety and Tolerability

• ALG.APV-527 demonstrated positive safety and tolerability across all cohorts
• A maximum tolerated dose has not been identified

 Evidence of favorable pharmacokinetics and biological activity of ALG.APV-527

• ALG.APV-527 could be measured in all patients with serum concentration of ALG.APV-527 consistent with the administered dose and preclinical predictions. 
• Biomarker analyses confirm biological activity of ALG.APV-527

“4-1BB has been a target of interest—though with excess toxicity—for decades, and novel bispecific approaches like this will enable us to maximize anti-tumor immunity while limiting the systemic toxicity concerns that have plagued this key immune costimulatory receptor. With this backdrop, these Phase 1 interim results are very encouraging, with ALG.APV-527 showing a positive safety profile with 60% of evaluable patients achieving stable disease, meaning not progressing for variable time frames including one breast cancer patient being treated with monotherapy on study with SD for more than 11 months. We are excited to see signs of clinical activity, underscoring the potential of the drug to benefit patients with solid tumors in the clinical setting, supported by a positive safety and tolerability profile," stated Thomas Marron, MD, PhD, Professor in Immunology & Immunotherapy and in Medicine, Hematology and Medical Oncology at Icahn School of Medicine at Mount Sinai, participating Investigator of the trial.

Trial Overview
The ALG.APV-527 Phase 1 trial is a multi-center, multi-cohort, open-label dose-escalation trial that includes administration of ALG.APV-527 in up to six escalating dose levels in a 3+3 design*. The trial is enrolling adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 will be given intravenously once every two weeks. The trial is assessing the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527.

*The 3+3 design proceeds in cohorts of three patients treated at increasing dose levels. Dose escalation stops when at least two out of three or six patients experience dose limiting toxicities (DLTs) at that dose level.

About ALG.APV-527
ALG.APV-527 is a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4. This has the potential to be clinically important because 4-1BB can stimulate the immune cells (antitumor-specific T cells and NK cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. 5T4 is an oncofetal tumor associated antigen overexpressed on numerous solid tumors including non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer.

Preclinical studies, highlighting the differentiated design of the molecule that minimizes systemic immune activation, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in preclinical models, has been published in the peer-reviewed publication, Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR).