Memorandum

Adocia 1Q19 – Delays continue as Lilly arbitration decision set for 3Q19; Closed-loop trial of BC Lispro in Beta Bionics’ iLet underway; New Pramlintide Insulin co-formulation featured heavily; €29 million in cash – May 2, 2019

Executive Highlights

  • Adocia gave its 1Q19 update via press releaseand accompanying slide deckThe company finished 1Q19 with €29 million in cash and cash equivalents, continuing a downward trend from €44 million in 3Q18and €40 million in 4Q18. However, this does not include an $11.6 million payment due from Lilly after courts ruled in favor of Adocia on the first arbitrationover BioChaperone Lispro (a modified biosimilar of Lilly’s Humalog). Currently outstanding in the second arbitration, set for a 3Q19 decision, are Adocia’s additional damages claim of ~$1.3 billion and Lilly’s counterclaim of ~$188 million. 
  • A phase 1 trial for ultra-rapid BioChaperone Lispro in a closed-loop system (Beta Bionics’ iLet pump and algorithm + Dexcom CGM) began in 1H19 (slide 16; first announced in 4Q18).While we don’t see the trial posted on ClinicalTrials.gov, we’re eager to see the results and compare them to Beta Bionics’ similar phase 2/3 trialwith insulin aspart. 
  • Additionally, a phase 2 bridging study for BC Lispro to confirm the manufacturing quality of active pharmaceutical ingredients (APIs) from recent partnerTonghua Dongbao (THDB) was delayed from 2Q19 to 3Q19.Assuming this study finds no difference from Lilly’s insulin lispro, Adocia plans to file for phase 3 initiation in the US and EU in 1Q20 – slightly back from the 4Q19 predicted in 4Q18. No bridging study is required to begin phase 3 in China, which is scheduled for 2019 and has an undisclosed milestone for Adocia attached. The company still plans to partner BC Lispro in regions outside of China, but it remains to be seen whether this partnership will come before or after phase 3.
  • THDB still plans to bring BC Combo (75/25 basal insulin glargine/prandial insulin lispro) through a bridging study in China during 2019,which will enable use of data from previous BC Combo development.Adocia is actively searching for partners for BC Combo in other markets. The company has valued the market in China, where premix insulin purportedly makes up 65% of the overall insulin market, at $5 billion (slide 18).
  • Adocia’s second pramlintide insulin candidate, ADO09, featured prominently in the company’s presentation following positive phase 1 results announced in April.A21G human insulin – a rapid-acting analog that is the main metabolite of Sanofi’s Lantus (insulin glargine) – replaces human insulin in the new co-formulation, which demonstrated a significant 85% decrease in blood glucose over the first two hours post-meal vs. Humalog (comparable to simultaneous, separate injections of Symlin and Humulin). Adocia’s first BC Pramlintide Insulin demonstrated a 97% reduction on this endpoint against Humalog in an identical phase 1 study in September 2018. Per Adocia management, ADO09 will be brought forward alone into additional studies for now; next up is a three-week phase 1/2 trial, expected to begin in 2H19, back from 2Q19 projected when results were first announced. Adocia is currently seeking partners globally.
  • No updates were given on BC Glucagon GLP-1 for obesity or BC Glucagon.The former is still set to enterphase 1 in 2H19 while the latter will enterphase 1/2 in 2H19, to our knowledge.

Adocia Diabetes/Obesity Pipeline Summary

The table below reflects the latest status, as far as we are aware, of Adocia’s diabetes/obesity-related pipeline products. Items highlighted in yellowindicate notable changes to the pipeline in recent months. 

Product

Indication

Status

Timeline/Notes

BioChaperone Lispro (ultra-rapid-acting insulin)

Type 1 and type 2 diabetes

Phase 3-ready

  • Phase 1 closed-loop trial began 1H19
  • Phase 2 bridging study to begin in 3Q19; phase 3 study filing (US/EU) planned for 1Q20; Phase 3 initiation in China expected in 2019
  • Secured Tonghua Dongbao as development and commercialization partner in China, retained rights to US, EU, Japan
  • Positive topline phase 1b results released in December 2017; Candidate showed significantly faster offset vs. Novo Nordisk’s Fiasp in first-ever head-to-head comparison of ultra-rapid-acting insulins 

HinsBet (rapid-acting human insulin)

Type 1 and type 2 diabetes

Phase 3-ready 

  • Adocia plans to license to a “regional player” in emerging markets for phase 3
  • Preclinical U500 formulation in development
  • Positive phase 2a results reported in 4Q16 

ADO09 (pramlintide/A21G human insulin)

Type 1 diabetes

Phase 1/2

  • Positive phase 1 results released April 2019
  • Phase 1/2 planned to begin 2H19

BioChaperone Pramlintide Insulin (pramlintide/human insulin) 

Type 1 diabetes

Phase 1/2

  • Deprioritized in favor of ADO09
  • Second Phase 1/2 trial scheduled to begin in 2Q19
  • Positive phase 1 results released in September 2018; Candidate conferred significant 97% reduction in postprandial excursions compared to Humalog

BioChaperone Combo (75/25 insulin glargine/insulin lispro premix)

Type 1 and type 2 diabetes

Phase 1

BioChaperone Glucagon (liquid-stable glucagon)

Ready-to-inject hypoglycemia rescue treatment (type 1 and type 2 diabetes); also in development for dual hormone AP (type 1 diabetes)

Phase 1

  • Final phase 1/2 trial initiation delayed to 2H19
  • Positive topline phase 1 results reported in 4Q17

BioChaperone Insulin Lispro/Pramlintide

Type 1 diabetes

Preclinical

  • Apparently de-prioritized in favor of human insulin/pramlintide combo
  • Phase 1 initiation delayed from “end of 2017” timeline
  • Added to pipeline in January 2017

BioChaperone Insulin Lispro/Exenatide

Type 2 diabetes

Preclinical 

BioChaperone Insulin Glargine/Liraglutide 

Type 2 diabetes

Preclinical

BioChaperone Insulin Glargine/Dulaglutide 

Type 2 diabetes

Preclinical

BioChaperone Glucagon GLP-1

Obesity 

Preclinical 

  • Phase 1 trials delayed to 2H19; adjacent with GLP-2 agonist teduglutide for SBS
  • Added to pipeline in January 2018 as one of Adocia’s first non-diabetes candidates

 

--by Peter Rentzepis, Ann Carracher, and Kelly Close