DEVELOPMENT PLAN


Xenikos has seen encouraging results in Phase 1/2 clinical testing. A Phase 3 registration trial in the U.S. is underway and a Phase 3 trial in Europe is planned. Clinical trial results and the Company’s development plans are described below.

Phase 1 dose escalation study
The safety and efficacy of T-Guard® was evaluated in a Phase 1 dose escalation study at the Radboud University Medical Centre in Nijmegen, the Netherlands. The main objectives of this study were to determine the pharmacokinetics, to detect any serious side effects and to evaluate to what extent T-Guard eliminates the T cells responsible for causing graft-versus-host disease (GVHD). The results showed a clear therapeutic window for T-Guard in the treatment of severe acute GVHD. The underlying rational behind T-Guard's mechanism of action and the study results of the first four patients were published in Blood, the medical journal of the American Society of Hematology.

Encouraging results from Phase 1/2 study
Xenikos completed a multi-center Phase 1/2 study evaluating T-Guard in patients who had received an allogeneic stem cell transplant for myeloid or lymphoid malignancies and had Grade II-IV steroid-resistant acute GVHD. Patients were treated with T-Guard administered as a four-hour intravenous infusion every 48 hours for a total of four infusions (4 mg/m2 each). The primary efficacy endpoint was defined as overall clinical response (ORR) on day 28. Main secondary endpoints were complete response (CR) rate at day 28 and six-month overall survival (OS), as well as safety and tolerability. 

Seventeen of the twenty patients in this study (85%) suffered from severe steroid-resistant acute GVHD (Grade III-IV), all had involvements of visceral organs; gut (18/20; 90%) and liver (5/20; 25%), and in 16/20 (80%) two or more organs were involved . Twelve of these patients (60%) achieved an ORR on day 28, with ten patients (50%) achieving a CR), which is remarkable considering the severity of the patient population. Twelve of the twenty patients (60%) were alive at six months (6-month OS). 

The outcomes compared favorably to the most recent historical controls of the participating centers, receiving either infliximab (N=21) or inolimomab/etanercept (N=21), where an ORR and CR was achieved in 52% and 19% of patients, respectively, and OS at six months was 29% for each of these groups. Notably, the two-fold difference in OS between T-Guard and the historical controls proved durable during the two-year follow up period.

The one-week treatment course resulted in profound in vivo T and NK cell depletion, followed by a rapid recovery of the immune system starting right after the last TGuard infusion with increasing T and NK cell numbers and a diverse T cell repertoire, suggesting a rebalancing of the immune system.

Treatment with a short course of T-Guard was generally well tolerated, with no significant infusion reactions. There were a limited number of potentially T-Guard-related adverse events, which, according to the treating physicians, were considered clinically well manageable and reversible after treatment. Data from the Phase 1/2 study were presented at the American Society of Hematology (ASH) Annual Meeting 2017 and have been published in the journal Biology of Blood and Marrow Transplantation.

Pivotal registration trials with the support of well-known transplant centers
Encouraged by the positive Phase 1/2 study results, T-Guard is currently being tested in a phase 3 trial in the US with the support of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Preparations for an EU pivotal study are underway. Xenikos has been working closely with regulatory authorities with regard to the design of these trials.

Additional opportunities in GVHD
If T-Guard is successful in treating second-line acute GVHD, it is envisioned that it could potentially be applied earlier in the course of the disease. There are an increasing number of biomarkers being developed and validated that can be used to identify acute GVHD patients who are at high risk of not responding to steroid treatment. For these patients, it could make sense to add T-Guard in combination with first-line steroid treatment, to prevent irreparable damage to the organs and immune system. In this setting, the short duration and targeted nature of T-Guard treatment could also enable intervention at an early stage of the disease, without inducing deep and long-term immunosuppression.  

Based on the results observed to date, Xenikos believes that T-Guard has the potential to offer a curative approach using a single-week treatment. In contrast to approaches to improve the symptomatic treatment of patients, T-Guard aims to restore the immunological balance, providing a durable remedy for patients with this devastating and potentially lethal disease.

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