Our AtD program
AtD, the most severe and common type of eczema, is a chronic relapsing inflammatory skin disease that causes severe itch, dry skin and rashes, predominantly on the face, inner side of the elbows and knees, and on hands and feet. Scratching of the afflicted skin leads to a vicious cycle causing redness, swelling, cracking, scaling of the skin and an increased risk of bacterial infections. Lichenification, thickening of the skin, is characteristic in older children and adults. The National Eczema Association estimates that AtD affects over 30 million Americans or up to 25% of children and 2-3% of adults. Sixty percent of AtD patients are diagnosed in the first year of life, and 90% of patients have a disease onset before age five. Symptoms commonly fade during childhood, however, approximately 10-30% of the patients will suffer from AtD for life. A smaller percentage first develop symptoms as adults.
Generic drugs are the approved standard of care, including immunomodulators cyclosporine and mycophenolate mofetil and topical treatments. There are disease-modifying biologics and small molecules currently in development, with dupilimab (targeting IL-4Rα) most recently approved.
MOR106 is a human monoclonal antibody designed to selectively target IL‑17C in clinical development worldwide. IL-17C as a target for AtD was discovered by us and has been shown to be distinct from other members of the IL-17 cytokine family, playing an important and pro-inflammatory role in certain skin disorders. MOR106 potently inhibits the binding of IL-17C to its receptor and thus inhibits its biological activity.
MOR106 arises from an alliance between us and MorphoSys, in which both companies contributed their core technologies and expertise and equally shared costs and benefits. In July 2018, we and MorphoSys announced that we entered into a collaboration regarding MOR106 with Novartis.
We evaluated MOR106 in a randomized, double-blind, placebo-controlled Phase 1 trial, with the first part evaluating single ascending doses (SAD) followed by multiple ascending doses (MAD) compared to placebo in approximately 25 patients with moderate to severe AtD in several European centers. Topline results of the complete trial were reported in September 2017. In the MAD portion with MOR106 in patients, all adverse drug reactions observed were mild-to-moderate and transient in nature and did not lead to clinically relevant safety signals. No serious adverse events and no infusion-related reactions were recorded.
Even though the trial was not statistically powered to show differences in efficacy between treatment groups, at the highest dose level of MOR106, in 83% of patients (five out of six) an improvement of at least 50% in signs and symptoms of AtD measured by the Eczema Area and Severity Index (EASI-50) was recorded at week four. The onset of activity was rapid and occurred within a few weeks and was maintained for over two months after the last treatment. Among patients receiving placebo, in 17% of patients (one out of six) an EASI-50 improvement was seen at week four.
As reported at AAD 2018, the pooled, mean EASI scores over time versus placebo show a sustained effect for weeks after completion of dosing:
EASI, % change from baseline, pooled data, median
Following the results of MOR106, together with Morphosys and then Novartis, we established a Phase 2 development program to enable a Phase 3 program that will be conducted by Novartis. We conduct all of the Phase 2 clinical research, with funding from Novartis.
We initiated the Phase 2 IGUANA trial with MOR106 in May 2018. This trial is aimed at evaluating various dosages and administration frequency. In the IGUANA Phase 2-trial, approximately 240 patients with moderate-to-severe AtD are treated over a 12-week period with one of three different intravenous doses of MOR106 (1, 3 or 10 mg/kg) or placebo using two different dosing regimens, in multiple centers across Europe. The placebo controlled, double-blind study will evaluate the efficacy, safety and pharmacokinetics of MOR106. Dosing at two or four-week intervals will be evaluated over the 12-week treatment period, followed by a 16-week observation period. The primary objective will be assessed by the percentage change from baseline in EASI score at week 12.
IGUANA Phase 2 trial
- ~240 patients with moderate-to-severe AtD
- IV infusion at 2 or 4 week intervals for 1 & 3 mg/kg
- IV infusion at 2 week interval for 10 mg/kg
- Recruitment in Europe
- Primary endpoint: % change from baseline in EASI score at week 12
We expect to report the primary analysis from IGUANA in 2019.
In September 2018 we initiated a Phase 1b bridging trial testing a subcutaneous formulation of MOR106. This bridging trial is a parallel-design Phase 1 clinical trial conducted in two parts. Part 1 is a single center, randomized, open-label trial in healthy volunteers who are treated with different single dose levels of MOR106 administered subcutaneously or intravenously. Part 2 is a multiple center, randomized, placebo-controlled, multiple dose trial in patients with moderate to severe AtD who will be treated subcutaneously for 12 weeks. Safety and tolerability, pharmacokinetics and occurrence of anti-drug-antibodies after administration of MOR106 will be assessed as endpoints. In addition, the efficacy of MOR106 will be explored in subjects with moderate to severe AtD.
MOR106 Phase 1b bridging trial
- Primary endpoints: safety, tolerability, PK
- Recruitment in EU
- Secondary endpoints Part 2: EASI/other efficacy scores, patient reported outcomes
We expect to report the topline results of this trial in 2019.
We initated a Phase 2 trial testing a subcutaneous formulation of MOR106 in combination with topical corticosteroids in patients with moderate to severe AtD. This trial, called GECKO, aims to randomize 60 patients who receive either a dose of MOR106 or placebo subcutaneously for 8 weeks, together with topical steroids, with a 16 week follow-up period foreseen. The primary endpoint of GECKO is the incidence of treatment emergent adverse events and severe adverse events through day 169.
Pharmacokinetics and occurrence of anti-drug-antibodies after administration of MOR106 will be assessed as secondary endpoints. In addition, the efficacy of MOR106 will be explored.
GECKO Phase 2 trial
- Patients with moderate-to-severe AtD, remain on topical steroid
- Double (loading) dose on day 1 only
- Primary endpoint: incidence of TEAEs and SAEs through day 169
- Secondary measures: PK & immunogenicity
- Exploratory measures: EASI and other efficacy scores
- Recruitment in Canada & U.S.