Memorandum

Adocia 1Q16 – Positive phase 1b results for BioChaperone Lispro vs. Humalog; New phase 1b trials for BioChaperone Lispro and HinsBet – April 18, 2016

Executive Highlights

  • Adocia and Lilly recently reported positive topline results from a phase 1b trial showing superior postprandial control (31-42% reduction in two-hour excursions) with ultra-rapid-acting BioChaperone Lispro vs. Lilly’s Humalog (insulin lispro) in patients with type 1 diabetes.
  • Adocia and Lilly have initiated a phase 1b trial of BioChaperone Lispro in healthy Japanese subjects, and Adocia has launched a new phase 1b trial of HinsBet (BioChaperone human insulin) in type 1 diabetes.

Adocia provided its 1Q16 update last week in a press release; the corporate presentation on its website has not yet been updated since February. See below for our top five highlights from the quarter.

1. Adocia and Lilly recently reported positive topline results from a phase 1b trial showing superior postprandial control with ultra-rapid-acting BioChaperone Lispro vs. Lilly’s Humalog (insulin lispro) in patients with type 1 diabetes.

2. Adocia and Lilly have initiated a phase 1b trial of BioChaperone Lispro in healthy Japanese subjects.

3. Adocia plans to launch three clinical studies of its proprietary ultra-rapid-acting insulins (BioChaperone Combo and HinsBet) in 2Q16.

4. Adocia has formed a Global Diabetes Medical Advisory Board led by the esteemed Dr. Jay Skyler (University of Miami, FL).

5. Adocia had cash and cash equivalents of €64.2 million (~$73.1 million) as of March 31, down from €72.1 million (~$78.4 million) at the start of the year.

Top Five Highlights

1. Adocia and Lilly recently reported positive topline results from a phase 1b trial showing superior postprandial control with ultra-rapid-acting BioChaperone Lispro vs. Lilly’s Humalog (insulin lispro) in patients with type 1 diabetes. The double-blind crossover study enrolled 36 patients with type 1 diabetes who were randomized to one of two treatment sequences (14 days with BioChaperone followed by 14 days with Humalog or vice versa) and one of three administration times (15 minutes before mealtime, at mealtime, or 15 minutes after mealtime). At the beginning of each treatment period, BioChaperone Lispro demonstrated a significant 31% reduction in two-hour postprandial excursions vs. Humalog when injected at mealtime. That reduction increased to 42% at the end of the 14-day treatment period. Both treatments were well tolerated, with similar adverse event rates between groups. Adocia’s announcement emphasized that these are the first safety results for BioChaperone Lispro in an outpatient setting. While the magnitude of the reduction in postprandial excursions was smaller in this trial than in a previous phase 1b trial (61% reduction vs. Humalog after a single meal – we aren’t sure from what baseline), the results support the potential for significantly faster action and more flexible dosing with BioChaperone Lispro vs. existing mealtime insulins. We see the ability to dose at mealtime as very helpful for manypatients and are especially curious to see the results for post-meal dosing.

2. Adocia and Lilly have initiated a phase 1b trial of BioChaperone Lispro in healthy Japanese subjects. The double-bind crossover trial aims to enroll 15 participants who will be randomized to receive either three single doses of BioChaperone Lispro (0.1, 0.2, and 0.4 U/kg) or one single dose of Humalog (0.2 U/kg) and two single doses of BioChaperone Lispro (0.1 and 0.2 or 0.2 and 0.4 U/kg) on three separate visits while undergoing a euglycemic clamp. The primary endpoint is area under the serum insulin concentration curve in the first 30 minutes after dosing; the study will also investigate pharmacodynamics (area under the glucose infusion rate time curve over eight hours) and adverse event rates. The trial began in January and is expected to complete this month. Adocia’s announcement notes that this study should allow the inclusion of Japanese patients in the phase 3 program for BioChaperone Lispro; it adds to what is already quite a comprehensive phase 1/2 development program for the product.

  • Two additional phase 1/2 trials for BioChaperone Lispro remain ongoing. One study (n=50) is investigating postprandial control vs. Humalog in patients with type 2 diabetes, and another study (n=36) is investigating postprandial control and a variety of PK/PD parameters vs. Humalog in pumps in patients with type 1 diabetes. Both trials had expected primary completion dates in January 2016, so we assume results should be arriving shortly.

3. Adocia plans to launch three clinical studies of its proprietary ultra-rapid-acting insulins (BioChaperone Combo and HinsBet) in 2Q16. Last week, the company announced the initiation of a randomized, double-blind phase 1b crossover study evaluating postprandial control with single doses of HinsBet (BioChaperone human insulin) vs. Lilly’s Humalog and Humulin (human insulin) in 36 patients with type 1 diabetes. The primary endpoint is blood glucose concentration one hour after the beginning of a standardized meal. Secondary endpoints include other PK/PD parameters, adverse event rates, and tolerability. The trial is not yet recruiting participants and is expected to complete in August 2016. Previous phase 2a results for HinsBet demonstrated a significantly faster action profile vs. Humulin and a comparable profile to Humalog. We assume the company intends to position the product as a cheaper alternative to currently marketed rapid-acting analogs – something that is sorely needed in an era of skyrocketing insulin costs. Adocia also noted in the 1Q16 update that it plans to launch two studies of BioChaperone Combo (insulin glargine/insulin lispro) in 2Q16. We continue to wonder if either of these products could be incorporated into the Lilly partnership if results look promising. Adocia also confirmed that the phase 3 study of BioChaperone PDGF-BB for diabetic foot ulcers in India is still expected to report results in mid-2016.

4. Adocia has formed a Global Diabetes Medical Advisory Board led by the esteemed Dr. Jay Skyler (University of Miami, FL). The board consists of nine highly respected endocrinologists from the US and Europe: Drs. Vanita Aroda (MedStar Health Research Institute, Hyattsville, MD – she is highly respected and took over a number of trials for Dr. Bob Ratner when he moved to ADA); Bruce Bode (Emory University, Atlanta, GA), John Buse (UNC, Chapel Hill, NC), William Cefalu (Pennington Biomedical Research Center, Baton Rouge, LA), Dan Einhorn (UCSD, San Diego, CA), Vivian Fonseca (Tulane University, New Orleans, LA), Chantal Mathieu (University Hospital of Leuven, Belgium), and Denis Raccah (APHM, Marseille, France) in addition to Dr. Skyler. The board’s immediate focus will be on the development of BioChaperone Combo – presumably, this will include a search for a partner.

5. Adocia had cash and cash equivalents of €64.2 million (~$73.1 million) as of March 31, down from €72.1 million (~$78.4 million) at the start of the year. The company recorded €2.7 million (~$3 million) in licensing revenue from Lilly in 1Q16, reflecting a portion of the $50 million upfront payment it received upon signing the BioChaperone Lispro deal.

--by Emily Regier and Kelly Close