API TECHNOLOGY PLATFORM
API’s Alpha Particle Immunotherapy (APIT) platform is a highly potent and selective form of targeted radiotherapy. It is based on attaching powerful alpha emitting radioisotopes Actinium 225 or Bismuth 213 to monoclonal antibodies (mAbs) which are large molecules capable of binding specifically to cancer cells.  By virtue of carrying alpha emitters, mAbs bring them directly to cancer cells where alpha emitters can selectively kill the targeted cell.  Figure below presents a schematic of a drug based on the Company’s APIT technology

The power of alpha emitters is best understood when compared to beta emitters, an alternative form of radioisotope used in cancer drugs.  The killing power of a radioactive particle i s directly proportional to its energy and inversely proportional to its range.  Alpha particle carries the most energy but travels the shortest path, while beta particle has less energy but goes farther in the body.  

Comparison between α and β irradiation’s effect on cancer cells and healthy tissues

Being 100 times more powerful than beta particles, alpha therapy is effective in cancers that are not sensitive to beta irradiation.  Prime examples are the past and current clinical trials in AML.  APIT has demonstrated extremely high cancer cell kill levels even though AML is not considered particularly radiosensitive and radiotherapy is not used in treating the disease.  Based on these inherent isotope traits, the Company and Dr. David Scheinberg, Chairman of the Molecular Pharmacology and Chemistry Program at MSKCC, API’s key scientific collaborator, developed alpha particles as an ideal payload for targeted cancer radiotherapy.  While their potency which is 100-fold higher than beta’s and cytotoxins’ significantly increases the killing power of alpha particle drugs against targeted tumor cells, their extremely short range limits any damage inflicted on healthy tissues.

In addition to its potency and range of emission, there are other key considerations for evaluating the suitability of particular radioisotopes for medical use.  Among them are half-life of the isotope, which is an indication of the period over which it remains radioactive, and its pharmacokinetics, i.e.  its distribution in the body and its eventual elimination from it.  For these reasons, Actinium 225 (Ac-225) and the isotope derived from it, Bismuth 213 (Bi-213), were selected as lynchpins of the Company’s technology.  Both isotopes have relatively short half-lives and favorable and controllable pharmacokinetics.  However, for efficacy, logistics and cost reasons API has decided to focus its efforts on Actinium 225 which has a 10 day half life v/s Bismuth-213’s half life of 46 minutes.