Memorandum

Adocia 4Q16 – Solid €58 million (~$64 million) cash position; Main priority is advancement of BioChaperone Lispro into phase 3 – February 16, 2017

Executive Highlights

  • Adocia’s 4Q16 and full year update highlighted the advancement of BioChaperone Insulin Lispro into phase 3 as the company’s main priority. The product’s licensing partnership with Lilly was recently terminated, and Adocia stated at the time that it intends to continue preparations for phase 3 while seeking a new clinical partner.

Adocia provided its 4Q16 and full year update via press release yesterday. The brief update focused almost exclusively on Adocia’s financials, noting the company’s solid cash position of €58 million (~$64 million) as of December 31, 2016, flat from 3Q16 and down from €72 million (~$78.4 million) at the end of 2015. Adocia additionally noted that its main priority is to advance its ultra-rapid-acting insulin candidate BioChaperone Insulin Lispro into phase 3 trials. As a reminder, BioChaperone Lispro was previously being developed in partnership with Lilly until, in an unexpected announcement at the end of January, Lilly terminated the licensing agreement in favor of the development of its own internal ultra-rapid insulin lispro candidate. The rights for BioChaperone Lispro have now reverted back to Adocia – at the time of the termination announcement, Adocia shared its intention to continue preparations for phase 3 while seeking a new clinical partner. Adocia management emphasized in a conference call recently after the announcement of the partnership termination that Lilly’s decision was grounded purely in economics and should not reflect negatively on the clinical profile of the BioChaperone candidate. “There is no question about the quality of our candidate,” management noted, highlighting the room for innovation that exists in the $7 billion rapid-acting insulin market. Refer to our full coverage of the termination of this licensing partnership for more information.

  • Adocia’s 4Q16 update was silent on other products in the company’s extensive diabetes pipeline, but we heard detailed updates on this during the company’s corporate update presentation in mid-January. The corporate update reaffirmed the company’s exclusive commitment to diabetes and announced a new business model focused on solidifying partnerships for its products as they approach late-stage clinical development. Below we outline Adocia’s extensive portfolio of clinical and preclinical programs utilizing the company’s proprietary BioChaperone technology (which stabilizes peptides to facilitate combination with other compounds), with specific details on the timing of each project’s progression. Slides 7 and 42 of the presentation for a visual overview of the company’s clinical program.
  • Adocia’s clinical program currently includes three innovative insulin products: BioChaperone Lispro, BioChaperone Combo (insulin glargine/insulin lispro), and HinsBet, a rapid-acting formulation of human insulin.
    • Adocia’s ultra-rapid-acting BioChaperone Lispro has undergone six positive phase 1/2 studies and is ready for advancement into phase 3. In the corporate update, Adocia expressed strong optimism and enthusiasm for the prospects of BioChaperone Lispro and for its partnership with Lilly in particular, which makes Lilly’s decision to terminate the partnership days later all the more disappointing for Adocia. All in all, though, the phase 1b data for the candidate presented at ADA 2016 were promising and we’re hopeful that Adocia will find a new clinical partner for the candidate.
    • BioChaperone Combo is currently being investigated in a phase 1b trial in people with type 2 diabetes, to complement existing positive results in people with type 1 diabetes presented at ADA 2016. Adocia expects results from this trial in 1Q17 (expected completion March 2017 according to ClinicalTrials.gov). Adocia has two more studies of BioChaperone Combo planned – a dose-response study (slated for 2Q17) and a brief two-week outpatient study (slated for 4Q17) – all intended to prepare for submission for entry into phase 3.
    • Adocia reported positive phase 2a results for HinsBet in October 2016. The study (n=36) was a randomized, double-blind, three-treatment, three-period cross-over trial comparing the effectiveness of HinsBet (BioChaperone human insulin) on post-meal glycemic control versus Lilly’s Humulin (human insulin) and Humalog (insulin lispro). During the first hour after a meal, HinsBet significantly reduced glucose excursion vs Humulin (p-0.0002) and was not significantly different from Humalog (p=0.5373). See slide 24 for the full data.
  • Management also reviewed Adocia’s extensive pipeline of preclinical programs, including several recently-announced BioChaperone-based projects expected to enter clinical trials this year: (i) co-formulation of insulin glargine with liraglutide (Novo Nordisk’s GLP-1 agonist Victoza); (ii) co-formulation of insulin glargine with dulaglutide (Lilly’s GLP-1 agonist Trulicity); (iii) co-formulation of insulin lispro with pramlintide (AZ’s amylin analogue Symlin); (iv) co-formulation of insulin lispro with exenatide (AZ’s GLP-1 agonist Byetta); and (v) liquid-stable glucagon.
    • At least one of Adocia’s BioChaperone basal insulin/GLP-1 agonist products is expected to enter phase 1 studies in 2017. With these new candidates – co-formulation of insulin glargine with liraglutide, (Novo Nordisk’s Victoza) dulaglutide (Lilly’s Trulicity), both of which were first announced in September 2016 – Adocia will enter the competitive landscape for basal insulin/GLP-1 agonist combinations, which currently features Novo Nordisk (Xultophy, once-daily), Sanofi (Soliqua, once-daily), Lilly, PhaseBio, and AntriaBio (all with once-weekly formulations in their preclinical pipelines). 
    • At least one of Adocia’s BioChaperone rapid-acting insulin combination products is expected to enter phase 1 studies in 4Q17. First announced in January 2016, the insulin lispro/pramlintide (AZ’s amylin analogue Symlin) product is intended for people with type 1 diabetes and the insulin lispro/exenatide (AZ’s GLP-1 agonist Byetta) product is intended for people with type 2 diabetes. To date, Adocia’s candidates represent the only rapid-acting insulin/pramlintide and rapid-acting insulin/GLP-1 co-formulations currently in development, and the only rapid-acting insulin co-formulation products in general for that matter (both the recently-approved Xultophy [Tresiba/Victoza] from Novo Nordisk and Soliqua [Lantus/lixisenatide] from Sanofi are basal insulin combinations). Given that the non-insulin biologics in these combinations are noted for their postprandial glucose lowering effect, we’re curious if these combination products could serve as “next-generation” prandial insulins in a sense by providing greater postprandial control than is currently offered by standalone rapid-acting insulins.
    • BioChaperone human glucagon is expected to enter phase 1 studies in 2017 (1H17, according to Adocia’s 2Q16 update). First announced in June, this project aims to develop an aqueous formulation of human glucagon for the rescue treatment of severe hypoglycemia and for use in a dual hormone closed-loop system. Several other soluble glucagon formulations are in more advanced stages of development, including Zealand’s dasiglucagon (recently completed phase 2), Xeris’ line of G-Pen glucagon autoinjectors (phase 3), and Lilly’s soluble glucagon candidate (phase 1). See our glucagon competitive landscape for a complete overview.

 

-- by Abigail Dove, Helen Gao, and Kelly Close