1. M E M O R A N D U M
Adocia announces positive phase 2a results for HinsBet (BioChaperone
human insulin) - February 10, 2015
Executive Highlights
▪ Adocia announced positive results recently from a phase 2a trial of HinsBet (BioChaperone human
insulin) showing a significantly faster onset of action vs. Lilly's human insulin Humulin and a
comparable early action profile to Lilly's Humalog (insulin lispro).
▪ Adocia also announced plans to develop a U500 concentrated formulation of HinsBet for patients
with severe insulin resistance.
Adocia announced positive results last week from a phase 2a trial of HinsBet (fast-acting BioChaperone
recombinant human insulin) showing a significantly faster action profile vs. Lilly's Humulin (recombinant
human insulin) and a comparable (!) profile to Lilly's Humalog (insulin lispro). The double-blind crossover
study (ClinicalTrials.gov Identifier: NCT02213146) enrolled 36 patients with type 1 diabetes who received
0.2 U/kg doses of HinsBet, Humulin, or Humalog under euglycemic clamp conditions. Results showed a
70% increase in insulin exposure in the first hour post-administration with HinsBet vs. Humulin as well as a
70% shorter onset of action (28 vs. 49 minutes) and double the metabolic effect in the first hour as measured
by glucose infusion rate (p<0.0001 for all findings). Total insulin exposure and potency were comparable
between the two products.
The press release characterized HinsBet's clinical profile in the first hour post-injection as comparable to
Humalog's. There was no significant difference in insulin exposure during the first thirty minutes or early
metabolic effect in the first hour between HinsBet and Humalog. The topline data did not include
information on total insulin exposure or any information on the PK/PD comparison beyond one hour. We
will be interested when the full results come out to see if HinsBet is as fast-off as Humalog, a factor which is
important to avoid postprandial hypoglycemia (which is still very hard to do). Adocia also plans to conduct
a meal study that would aim to demonstrate comparable postprandial control with HinsBet vs. an insulin
analog administered before the meal.
Adocia appears to be positioning HinsBet as an alternative to currently marketed rapid-acting analogs -
but presumably cheaper. It is unlikely that HinsBet's action profile could match that of Adocia/Lilly's
BioChaperone Lispro (which received significant attention during Lilly's 4Q14 update and demonstrated a
faster-on, faster-off profile than Humalog) or other ultra-rapid-acting insulin analogs. Rather, the
product's advantage appears to come from a cost angle. We are curious as to how the economics of a faster-
acting human insulin formulation compare against a clinically comparable biosimilar of an existing off-
patent rapid-acting analog such as Humalog. One potential advantage according to Adocia is that HinsBet
could likely be produced using existing manufacturing facilities for human insulin whereas manufacturing
a biosimilar analog would require investment in new equipment. Fascinating … Sanofi's biosimilar insulin
lispro recently entered phase 3 and Biocon has preclinical formulations of both insulin lispro and insulin
aspart (Novo Nordisk's NovoLog patent protection expires in 2017, while Humalog's expired in 2013).
▪ We were excited to hear that Adocia is also developing a concentrated U500
formulation of HinsBet for patients with severe insulin resistance. Lilly's Humulin U500
is essentially the only currently available treatment option for patients with high daily insulin
requirements; the product has performed well in recent quarters, which is not surprising given the
rise in severe obesity. Other alternatives in development include Biodel's phase 2a BIOD-531 (ultra-
rapid-acting U400 human insulin) and Thermalin's preclinical Fluorolog (U500 rapid-acting insulin
www.closeconcerns.com 1

2. analog). As Adocia's press release notes, Humulin U500 has a substantially slower action profile
compared to Humulin U100, meaning there is a significant unmet need for truly rapid-acting
concentrated insulin formulations.
--by Emily Regier, Manu Venkat, and Kelly Close
www.closeconcerns.com 2