Memorandum

Transition Therapeutics F4Q14 – Lilly initiates phase 2 trial for partnered GLP-1/glucagon dual agonist TT401 – October 9, 2014

Executive Highlights

  • Lilly has commenced a phase 2 trial of TT401, Lilly and Transition’s partnered once-weekly GLP-1/glucagon dual agonist; estimated primary completion date of May 2015.

Transition Therapeutics reported financial results for F4Q14 (calendar 2Q14) in a call led by CEO Dr. Tony Cruz last month. The central diabetes-related highlight was the news that partner Lilly has commenced a phase 2 trial (ClinicalTrials.gov Identifier: NCT02119819) of TT401 (LY2944876), the companies’ partnered once-weekly oxyntomodulin analog (GLP-1/glucagon dual agonist) – this is in line with guidance from Transition’s April pipeline update indicating that dosing for the trial would begin in 2Q14. The study, which began in mid-May, aims to enroll up to 375 patients with type 2 diabetes, who will be randomized to receive one of four doses of TT401, once-weekly exenatide (AstraZeneca’s Bydureon), or placebo. The trial will consist of an initial 12-week double-blind period followed by a 12-week open-label period. The primary endpoint is change in A1c at 12 weeks, and secondary endpoints include change in A1c at 24 weeks and change in body weight at 12 weeks; primary completion is expected in May 2015.

Between the end of June and the time of the call, the trial crossed the 20% enrollment milestone. As a result, Lilly paid Transition the first installment of a $6 million milestone payment. For background, Lilly exercised its option to license TT401 in the summer of 2013 and awarded Transition a payment of CAD 7.1 million (~$6.4 million). As of September 25, Transition had CAD 43.5 million (~$38.6 million) in cash on hand, which management said would be sufficient to fund operations well beyond the next 12 months.

  • During the call, management reiterated the possibility that dual agonists such as TT401 can deliver superior weight loss and/or better glucose control relative to GLP-1 single agonists. According to management, Lilly and Transition selected AZ’s Bydureon as a comparator for the ongoing phase 2 trial partially in order to provide guidance on TT401’s commercial potential vs. currently marketed GLP-1 agonists.
  • Management announced during the call that Transition plans to license one or two additional molecules within the next year; there has been no indication thus far as to what disease areas are under consideration.
  • Lilly’s pipeline also includes another phase 2 GLP-1/glucagon dual agonist, oxyntomodulin. Other companies developing GLP-1/glucagon dual agonists include Xenetic Biosciences (phase 1), Hanmi Pharmaceuticals (phase 1), Zealand/BI (Zealand now has sole rights to phase 1 candidate ZP2929; BI selecting new lead candidate for partnership), and Prolor/OKPO (preclinical).

Questions and Answers

Q: Can you give any color on what you’re looking at as far as your potential pipeline?

A: In the past, we would license a molecule and bring that in-house and then de-risk it. As part of the strategy going forward, we’ve decided to spend time investigating those molecules and de-risking them before we actually license them. We’re in the process of doing that with two molecules. At this time, it’s still too early to identify whether those molecules are ones that we’re going to move forward. But once we’ve de-risked them and we think there’s a good enough risk-to-reward profile and commercial opportunity to move forward, then we will license those molecules. I would say we should have that completed between now and the end of the year at least for one of them, if not both. At this point it’s too early to say what the molecules are. We’d rather do the full analysis first before we determine that.

-- by Emily Regier, Manu Venkat, and Kelly Close