Memorandum

Adocia 2Q17 – New phase 2 study compares BioChaperone Lispro vs. Fiasp; Evaluation continues for BioChaperone Lispro partner; BioChaperone Glucagon enters phase 1; Strong €52 million (~$61 million) cash position – July 25, 2017

Executive Highlights

  • In Adocia’s 2Q17 update, management highlighted the company’s priority of advancing its ultra-rapid-acting insulin candidate BioChaperone Insulin Lispro into phase 3 trials. Evaluation continues for a new licensing partner (following Lilly’s unexpected termination of the previous agreement in January). In the meantime, Adocia has initiated a phase 2 study comparing the candidate to Novo Nordisk’s Fiasp (faster-acting insulin aspart) and NovoLog (insulin aspart). This marks the first trial to compare ultra-rapid-acting insulins head-to-head.
  • Positive phase 1/2 results demonstrated the superiority of BioChaperone Combo (insulin glargine/insulin lispro) vs. an existing pre-mix, Humalog Mix25. On the heels of this positive data, the company launched a phase 1b dose-response study to further prepare the candidate for entry into phase 3 trials.
  • In another exciting development, BioChaperone Glucagon was moved into phase 1 trials in 2Q17. By year-end, Adocia plans to begin phase 1 investigation of its BioChaperone insulin glargine/liraglutide co-formulation.

Adocia recently provided its 2Q17 update via press release. See below for our top five highlights from the update:

Top Five Highlights

1. Adocia reiterated that its main priority is to advance ultra-rapid-acting insulin candidate BioChaperone Insulin Lispro into phase 3 trials, highlighting to this end the initiation of a new phase 2 study comparing the candidate to Novo Nordisk’s Fiasp (faster-acting insulin aspart) and NovoLog (insulin aspart). 

2. On BioChaperone Combo (insulin glargine/insulin lispro), Adocia highlighted positive topline phase 1/2 results in type 2 diabetes: The candidate reduced postprandial glucose excursions by a statistically significant 18% vs. Humalog Mix25, and also resulted in significantly less hypoglycemia vs. Humalog Mix25. BioChaperone Combo was non-inferior to basal/bolus therapy with Sanofi’s Lantus and Lilly’s Humalog on these outcomes. A phase 1b dose-response study of BioChaperone Combo was also initiated in 2Q17 (on schedule), with data expected to read out in 4Q17.

3. Adocia reiterated its intention to license phase 3-ready HinsBet to a “regional player” in emerging markets to support continued development and hopeful launch of this rapid-acting human insulin.

4. Most notably, a phase 1 study of the company’s liquid-stable BioChaperone Glucagon candidate was launched in 2Q17 (on schedule). Adocia also shared that its BioChaperone insulin glargine/liraglutide co-formulation is expected to enter phase 1 by year-end, as is ≥one of its preclinical BioChaperone multi-hormonal/rapid-acting insulin combinations: insulin lispro/pramlintide (AZ’s amylin analogue Symlin) for type 1 diabetes and/or insulin lispro/exenatide (AZ’s GLP-1 agonist Byetta) for type 2 diabetes.

5. Adocia had cash and cash equivalents totaling €52 million (~$61 million) as of June 30, down from €58 million (~$67 million) in 1Q17 and €61 million (~$69 million) in 2Q16

Top Five Highlights

1. Laser Focus Remains on Phase 2 Ultra-Rapid-Acting BioChaperone Insulin Lispro

Adocia reiterated that its main priority is to advance its ultra-rapid-acting insulin candidate BioChaperone Insulin Lispro into phase 3 trials, highlighting to this end the initiation of a new phase 2 study comparing the candidate to Novo Nordisk’s Fiasp (faster-acting insulin aspart) and NovoLog (insulin aspart). BioChaperone Lispro was previously under development in partnership with Lilly until, in an unexpected announcement at the end of January, Lilly terminated this 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, and the company will continue preparations for phase 3 while seeking a new clinical partner. The new phase 2 study, initiated in June 2017, is the first clinical trial to examine two ultra-rapid insulin formulations head-to-head. It also marks the first study of BioChaperone Lispro since the termination of the licensing agreement with Lilly. With topline results expected by end of year, Adocia has expressed optimism that this clinical trial will underscore the value of BioChaperone Lispro (which has completed six positive phase 1/2 studies, including a particularly promising one presented at ADA 2016), perhaps helping to secure a new partner to advance the candidate into phase 3 trials.

  • The phase 2 study will compare the PK/PD profile of BioChaperone Lispro vs. Fiasp and NovoLog in participants with type 1 diabetes using an insulin pump (n=42). Participants will receive single doses (0.15 units/kg) of BioChaperone Lispro, Fiasp, and NovoLog via insulin pump on three separate dosing visits in a randomized, double-blind design. BioChaperone Lispro has demonstrated an accelerated insulin action profile vs. traditional prandial insulins in multiple phase 1 and 2 studies, in people with both type 1 and type 2 diabetes, using both insulin pumps and syringes. Now, we’re eager to see how the candidate stacks up against another ultra-rapid-acting insulin, especially since marketing around Fiasp has also emphasized the faster-on, faster-off nature of the product. EMA approved in January 2017 and pending an FDA decision on its Class II resubmission  (expected in 3Q17), Fiasp is a first-in-class ultra-rapid-acting insulin, and stands to be one of BioChaperone Lispro’s biggest commercial competitors (along with Lilly’s internally-developed candidate) should it progress into phase 3 development and eventually reach the market.
  • We see plenty of room for innovation in the rapid-acting insulin market, which fell 5% YOY to $6.1 billion in 2016, due in part to intense competitive pressure from GLP-1 agonists and SGLT-2 inhibitors (both therapy classes address postprandial excursions). We especially see upside for faster-acting insulins in pumps and closed loop systems, and also to reduce hypoglycemia through faster-onset, faster-offset – what is currently accessible to the vast majority of patients leaves far too much room for hypoglycemia risk. In Adocia’s 1Q17 earnings update, management noted that the company will be closely observing how Fiasp fares in the challenging commercial landscape for insulin products. We certainly hope to see continued development of BioChaperone Lispro, and we’ll keep our fingers crossed for a strong, strategic clinical partner. We see this ultra-rapid-acting insulin as a very valuable potential addition to the market.

2. Positive Phase 1/2 Results for BioChaperone Combo in Type 2 Diabetes

On BioChaperone Combo (insulin glargine/insulin lispro), Adocia highlighted positive topline phase 1/2 results in type 2 diabetes: The candidate reduced postprandial glucose excursions by a statistically significant 18% vs. Humalog Mix25, and also resulted in significantly less hypoglycemia vs. Humalog Mix25. BioChaperone Combo was non-inferior to basal/bolus therapy with Sanofi’s Lantus and Lilly’s Humalog on these outcomes. This trial complements existing positive results for the candidate in people with type 1 diabetes, presented by Dr. Steve Edelman at ADA 2016. Based on these promising findings, Adocia launched a new phase 1b dose-response study of BioChaperone Combo in 2Q17, with data expected to read out in 4Q17. This comes right on schedule with the 2Q17 start outlined in the company’s 1Q17 earnings update. The study will assess the PK/PD profile of BioChaperone Combo at three different doses (0.6 units/kg, 0.8 units/kg, and 1.0 units/kg) vs. 0.8 units/kg Humalog Mix25 in people with type 2 diabetes (n=32). Adocia also reiterated that a two-week outpatient study is slated for a 4Q17 start – this and the dose-response study are meant to prepare the candidate for entry into phase 3. We imagine Adocia will look to partner for phase 3 development of BioChaperone Combo, but we have yet to hear any specifics on this front – it will be interesting to see if perhaps a single partner may look to scoop up Adocia’s entire BioChaperone portfolio.

3. Goal to License HinsBet (Rapid-Acting Human Insulin) to “Regional Player” for Emerging Markets

Adocia reiterated its intention to license phase 3-ready HinsBet to a “regional player” in emerging markets to support continued development and hopeful launch of this rapid-acting human insulin. 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 HinsBet (BioChaperone human insulin) vs. Lilly’s Humulin (human insulin) and Humalog (insulin lispro), and it met its primary endpoint of superior postprandial glucose control vs. Humulin on a one-hour meal test (p=0.0002). HinsBet was non-inferior to Humalog on this endpoint (p=0.5373).

4. Progress on BioChaperone Glucagon, Insulin Glargine/Liraglutide, Insulin Lispro/Pramlintide, Insulin Lispro/Exenatide

A phase 1 study of the company’s liquid-stable BioChaperone Glucagon candidate was launched in 2Q17, on track with Adocia’s planned timeline. The candidate is being developed as a rescue treatment for severe hypoglycemia and for use in a dual hormone closed loop system. This in-human phase 1 trial will assess the safety and PK/PD parameters of two different formulations of injectable BioChaperone Glucagon vs. Novo Nordisk’s GlucaGen rescue treatment in people with type 1 diabetes. Adocia’s candidate joins several other soluble glucagon formulations in development, including Zealand’s dasiglucagon (recently entered phase 3), 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.

  • Adocia also shared that its BioChaperone insulin glargine/liraglutide co-formulation is expected to enter phase 1 by year-end. We are interested to see how Adocia will fare in the competitive landscape for basal insulin/GLP-1 combinations. In addition to Adocia’s co-formulations of BioChaperone insulin glargine with liraglutide (Novo Nordisk’s Victoza) and dulaglutide (Lilly’s Trulicity), this landscape includes a phase 1 candidate from Lilly, as well as preclinical candidates from PhaseBio and AntriaBio. Novo Nordisk’s Xultophy and Sanofi’s Soliqua are fixed-ratio basal insulin/GLP-1 combos already on the market – Xultophy was first-to-market ex-US, though both products were FDA approved for the US on the same day in November 2016. It’s unclear what the dosing schedule for Adocia’s combinations will be, though the trend for “next-generation” basal insulin/GLP-1 combos seems to be once-weekly dosing to minimize injection burden and hopefully improve adherence. We’re curious how Adocia might position its own product given that insulin glargine and liraglutide will likely be off-patent by the time it reaches the commercial market. Perhaps Adocia will offer its combinations at a discount, as a kind of biosimilar, which would certainly be a big win for patients on the affordability/accessibility front.
  • At least one of Adocia’s preclinical BioChaperone multi-hormonal/rapid-acting insulin combinations – insulin lispro/pramlintide (AZ’s amylin analogue Symlin) for type 1 diabetes and/or insulin lispro/exenatide (AZ’s GLP-1 agonist Byetta) for type 2 diabetes – is also expected to enter phase 1 by the end of 2017. First announced in January 2017, 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. Given that the non-insulin biologics in these combinations are noted for their postprandial glucose-lowering effect, we’re curious if these 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. We’re especially intrigued about the potential effects of these agents on hypoglycemia – presumably, combination with gut peptides allows for a smaller dose of insulin lispro, which could reduce hypoglycemia risk.

5. Company Has Strong Cash Position with ~$61 Million

Adocia had cash and cash equivalents totaling €52 million (~$61 million) as of June 30, down from €58 million (~$67 million) in 1Q17 and €61 million (~$69 million) in 2Q16. Cash spent in the first half of 2017 amounted to €14 million (~$16 million), compared to €11 million (~$13 million) in the first half of 2016. Adocia attributed this increase in spending to the continued progress of many clinical development programs – all of which are now entirely financed by Adocia, contrary to last year before the termination of the partnership with Lilly. Overall, the company expressed optimism regarding its solid cash position, which will enable it to finance its entirely diabetes-focused portfolio – a portfolio we will continue to watch closely.

 

-- by Abigail Dove, Payal Marathe, and Kelly Close