APG2305, Allostera’s Lead Product

The Company's lead Allosteramer™, an oral IL23-receptor inhibitor, APG2305, targets an immune pathway which has recently been implicated as the principal regulator of autoimmune diseases. By shutting off the signal from IL23, APG2305 aims to eliminate the body's primary method of maintaining autoimmune diseases such as psoriatic arthritis, psoriasis, Crohn's disease, rheumatoid arthritis and over 60 other diseases. Allostera has proof-of-concept of the mechanism, activity and safety of APG2305 in several in vitro and animal models. The Company has begun a formal IND-enabling program of APG2305 (ADME, toxicology, PK, etc.) with the purpose of commencing a proof-of-concept clinical trial evaluating APG2305 in patients with psoriatic arthritis.

What is psoriatic arthritis?

Psoriatic arthritis (PsA), a painful form of psoriasis which involves inflammation of the joints (without rheumatoid factor) affects over 500,000 patients in the US alone. Like in other autoimmune diseases, agents used to treat PsA include steroids, TNF inhibitors and other inflammation blockers which have significant side effects, are often injectable and only work modestly to affect the disease. There is a significant need for new agents which offer three benefits to the patient: better efficacy, safety and administration.

Potential Benefits of APG2305

We believe APG2305 has the potential to offer all three benefits:

1. better efficacy because it is targeting the central immune pathway now known to regulate autoimmune diseases and should shut down the disease, not just the symptoms;
2. better safety because it is a specific IL23 inhibitor which, unlike other agents, should shut off the autoimmune disease while minimally affecting the overall immune system (infections and malignancy surveillance) for long-term chronic use; and
3. better administration because unlike other large molecules (such as monoclonal antibodies) which require intravenous infusions or subcutaneous injections, APG2305 is orally active.

Two injectable monoclonal antibodies, each targeting both IL23 and IL12 (a cytokine used in the pathway to fight tumors and infections), that are in development by other companies for psoriatic arthritis, psoriasis and Crohn’s disease, have shown results in Phase II and Phase III clinical trials that have been considered “dramatic”. Various parties, including FDA, have expressed concern that blocking IL12 for long periods of time may lower immune surveillance and cause higher risk of infections and possibly cancer. We believe an agent targeting only IL23 will have significant advantages (e.g., fewer infections), especially if delivered orally as opposed to an injection.