Immunotherapy
Platform
ACT-101

Immunotherapy Platform

Therapy Indication Partners Discovery Pre-Clinical Phase I Phase II
ACT-101
(AFP)
Autoimmune
Inflammatory Bowel Disease (Crohn's/Colitis)
 
Myasthenia Gravis (muscle weakness)
 
Hashimoto Disease
 
Multiple Sclerosis, Others
 

Myasthenia Gravis (MG) Antibodies

The Effect On Neuromuscular Junction

Normal Neuromuscular Junction

Motor neuron releases acetylcholine (ACh) which binds to nicotinic acetylcholine receptors (nAChRs) on the cell membrane of the muscle fiber resulting in muscle contraction.

Neuromuscular Junction In Myasthenia Gravis

In myasthenia gravis antibodies are produced that block the receptors (nAChRs) and result in the reduced transmission of nerve impulses (ACh) leading to weakness and fatigue in the affected muscles.

Anticipated Effect of AFP Treatment

It is anticipated that AFP will block the antibodes produced by myasthenia gravis and help restore the transmission of nerve impulses (ACh) and improve symptoms.

Target Product Profile

  • Direct autoantibody blocker with a unique mechanism of action (MOA)
  • Add-on to standard immunosuppressive therapies
    • Can be used in combination with other standard therapies as it is safer than immunosuppressives and has a different MOA
    • Can be used where steroid-sparing therapy is desired (young or old)
  • Convenient to use
    • Subcutaneous (SC) administration allows for self-administration (e.g. prefilled syringe)
    • May be able to move to less frequent dosing (once every 2 weeks) during a “maintenance phase”

PK Study Supporting Weekly Dosing

  • Binding inhibition of approx. 74% at 0.4 µg/mL
  • Serum concentration level in pregnancy (0.3 – 0.5 µg/mL) associated with remission
  • We can safely exceed this concentration based on PK data

Time-concentration curve of mean MM-093 serum levels after subcutaneous injection
with 21 mg of MM-093 once per week

Brenner Study

In Vivo Survival Study

  • EAMG - the “gold standard” model for MG
  • Induced by passive transfer of autoantibodies
  • Mouse AFP used to avoid immune response
  • Results suggest that chronic treatment with AFP needed to maintain benefits

Buschman et al 1987