Memorandum

Adocia 3Q16 – Phase 1 trial initiated for BioChaperone Combo (insulin glargine/insulin lispro); Diabetes portfolio expanded to include new programs for BioChaperone Basal GLP-1 and BioChaperone Human Glucagon – October 16, 2016

Executive Highlights

  • Adocia announced the initiation of a new phase 1 trial for BioChaperone Combo (insulin glargine/insulin lispro) in people with type 2 diabetes, with results expected in 1Q17. Additional trials are ongoing for BioChaperone Lispro and HinsBet, with results expected in 4Q16.
  • Adocia highlighted the addition of two new projects to its diabetes portfolio: BioChaperone Basal GLP-1 and BioChaperone Human Glucagon.
  • The phase 3 trial evaluating BioChaperone PDGF-BB for the treatment of diabetic foot ulcer failed to meet its primary endpoint, leading to discontinuation of its development.

Adocia recently provided its 3Q16 update via press release. Reported below are our top five highlights from the update.

1. Adocia announced the initiation of a new phase 1 trial for BioChaperone Combo (insulin glargine/insulin lispro) in people with type 2 diabetes. 

2. Consistent with the company’s strategic decision to commit itself exclusively to diabetes therapy, Adocia highlighted the addition of two new projects to its diabetes portfolio: BioChaperone Glargine GLP-1 (announced in September) and BioChaperone Human Glucagon (announced in June).

3. Results are expected in 4Q16 for ongoing clinical trials for two innovative new insulin formulations: BioChaperone Lispro, a Lilly-partnered rapid-acting formulation of insulin lispro, and HinsBet, a rapid-acting formulation of human insulin.

4. Very disappointingly, the phase 3 trial evaluating BioChaperone PDGF-BB for the treatment of diabetic foot ulcer failed to meet its primary endpoint, leading to discontinuation of its development.

5. Adocia had cash and cash equivalents of €57.5 million (~$64.1 million) as of September 30, down from €60.9 million (~$68.9 million) in 2Q16 and €68.7 million (~$77.2 million) in 3Q15.

Top Five Highlights

1. Adocia announced the initiation of a new phase 1 trial for BioChaperone Combo (insulin glargine/insulin lispro) in people with type 2 diabetes.  The study (n=36) will investigate postprandial glucose control in BioChaperone Combo vs. premix insulin (Lilly’s Humalog Mix25) or separate injections of Sanofi’s Lantus (insulin glargine) and Lilly’s Humalog (insulin lispro). Results are expected in 1Q17 (March 2017, according to ClinicalTrials.gov). Assuming positive results from the present study, we’re curious to see whether BioChaperone Combo could eventually be included in Adocia’s partnership with Lilly. The product has shown promising results so far – Adocia presented results at ADA 2016  demonstrating that the candidate produced lower post-meal glucose peaks (72 mg/dl vs. 95 mg/dl) and reduced postprandial glucose excursions at one hour (-24 mg/dl) compared to Lilly’s Humalog Mix in a double-blind, randomized, crossover mixed-meal study (n=28). Adocia has previously stated that it plans to launch two clinical studies of BioChaperone Combo in 2Q16 and we are curious what the timeline for the launch of the second trial looks like.

2. Consistent with the company’s strategic decision to commit itself exclusively to diabetes therapy, Adocia highlighted the addition of two new projects to its diabetes portfolio: BioChaperone Glargine GLP-1 and BioChaperone Human Glucagon. The BioChaperone Glargine GLP-1 project, announced this September, involves the development of two new basal insulin/GLP-1 agonist combination products: BioChaperone Glargine Dulaglutide (insulin glargine/dulaglutide) and BioChaperone Glargine Liraglutide (insulin glargine/liraglutide). Both products will utilize Adocia’s proprietary BioChaperone technology, which stabilizes insulin glargine (Sanofi’s Lantus) to facilitate combination with other compounds, in this case Lilly’s Trulicity (dulaglutide) and Novo Nordisk’s Victoza (liraglutide). Both would be once-daily products. Adocia shared that it expects to initiate a clinical trial involving a lead candidate in 2017 and suggested that development for these combinations will proceed relatively quickly given the well-characterized clinical efficacy and safety profiles of the two drug components. Furthermore, the BioChaperone Human Glucagon project, first announced in June, hopes 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. Clinical trials are slated to begin in 1H17, according to Adocia’s 2Q16 update. We’re excited to see Adocia’s continued investment in the diabetes field, though we’re curious to see how the company plans to differentiate its products. In particular, its basal insulin/GLP-1 agonist combination will arrive on the market many years after the launch of Novo Nordisk’s Xultophy (insulin degludec/liraglutide; expected to launch in the US in late 2016 or early 2017; already available in Europe) and Sanofi’s iGlarLixi (insulin glargine/lixisenatide; expected to launch in late 2016 or early 2017). 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), Lilly’s soluble glucagon candidate (phase 1), and Novo Nordisk’s glucagon analog (phase 1, though this will possibly be a longer-acting formulation with the potential for co-formulation with a GLP-1 agonist).

3. Results are expected in 4Q16 for ongoing clinical trials for two innovative new insulin formulations: BioChaperone Lispro, a Lilly-partnered rapid-acting formulation of insulin lispro, and HinsBet, a rapid-acting formulation of human insulin.

  • Results from an ongoing phase 1b trial in patients using BioChaperone Lispro in an insulin pump are expected in 4Q16. According to ClinicalTrials.gov, the trial is expected to complete this month, in October 2016. The trial (n=80) includes two parts. Part A involves a 14-day crossover trial (n=36) evaluating postprandial control and a variety of PK/PD parameters vs. Humalog in pumps in patients with type 1 diabetes. Part B (n=44) will evaluate PK/PD, pump compatibility, and safety of BioChaperone Combo vs. Humalog administered via two different pumps (Roche’s Accu-Chek Spirit and Medtronic Paradigm Veo) and administered via syringe in a four-period crossover study.
  • Results from the phase 1/2 HinsBet study are expected in the “next few weeks” – a slight delay from the original 3Q16 end date specified in Adocia’s last earnings update. The HinsBet study (n=36) is 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). ClinicalTrials.gov lists the trial as already having completed and we look forward to the topline results once the data analysis is completed.

4. Very disappointingly, the phase 3 trial evaluating BioChaperone PDGF-BB for the treatment of diabetic foot ulcer failed to meet its primary endpoint, leading to discontinuation of its development. The BioChaperone PDGF-BB study (n=252) was a multicenter, randomized, parallel group, double blind trial conducted in India comparing the effectiveness of BioChaperone PDGF-BB on foot ulcer wound closure, vs. the standard of care saline solution. After 20 weeks of treatment BioChaperone PDGF-BB did not demonstrate a significant improvement of wound closure compared to placebo. Adocia management cited the difficulty of obtaining a wound healing indication and the lack of standardized treatment for wounds, in addition to these negative clinical trial results, as contributing factors to the discontinuation of this candidate. We’re disappointed to hear this, given the unmet need in this area. Despite this setback, we’re glad to see Adocia reaffirm its commitment to diabetes with new investments in insulin, GLP-1 agonists, and glucagon.

5. Adocia had cash and cash equivalents of €57.5 million (~$64.1 million) as of September 30, down from €60.9 million (~$68.9 million) in 2Q16 and €68.7 million (~$77.2 million) in 3Q15. CFO Ms. Valerie Danaguezian noted that the cash position will progress to over €64 million (~$74.1 million) in early October following the collection of a research tax credit. Overall the company expressed optimism regarding its strong cash position, which will enable it to finance its now entirely diabetes-focused portfolio.

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