Memorandum

Adocia 2Q19 – ADO09 (pramlintide insulin) phase 1b trial starts; Cash and equivalents now at $23 million; No updates on other pipeline candidates  – July 17, 2019

Executive Highlights

  • Adocia gave its 2Q19 update via press release and accompanying slide deck today. The company closed out 2Q19 with €20.7 million (~$23 million) in cash and cash equivalents, showing a €19.2 million (~$21.8 million) decrease from 1Q19. This is also down from €44 million in 3Q18 and €40 million in 4Q18.  Of note, Adocia affirmed that it expects a decision in 3Q19 on the second phase of its ongoing arbitration with Lilly over BioChaperone Lispro.  

  • A phase 1b trial for the safety and efficacy of ADO09 (pramlintide insulin) in patients with type 1 is underway, and results are expected in 4Q19. Elsewhere in the pipeline, BioChaperone Pramlintide Insulin studies have been deprioritized to ensure sufficient resources for the ADO09 effort. There were also no further updates on studies involving BC Combo, BC Glucagon GLP-1 for obesity, BC Glucagon, or BioChaperone Lispro in a closed-loop system.

  • Adocia is still working with China-based Tonghua Dongbao (THDB) to initiate a phase 3 trial in China for BioChaperone Lispro in 2019. Efforts are currently being put toward completing qualification requirements to start the trials in China and other territories. There was no mention of phase 2 studies in the US/EU after delays reported in 1Q19.

See more on our top three highlights below, along with Adocia’s expected upcoming milestones:

 

 

Top Three Highlights

1. Adocia’s Pramlintide Insulin Candidate, ADO09, Progresses in Pipeline with 3-Week Phase 1b Trial; Prioritized over BioChaperone Pramlintide Insulin

With positive phase 1 results announced in April, a 3-week phase 1b trial on the safety and efficacy of ADO09 in patients with type 1 is underway with results expected in 4Q19. Adocia characterized these phase 1 results as “excellent” in its press release. ADO09 is Adocia’s second pramlintide insulin candidate, with A21G human insulin replacing traditional human insulin in the co-formulation. The phase 1b trial was initiated in June 2019, and the primary outcome is the comparison between post-meal glucose profiles after bolus of ADO09 versus Novo Nordisk’s rapid acting insulin NovoLog. All participants will be given standardized mixed meals at the end of a 24-day long multiple daily injection of either compound. Phase 1 results shared in 1Q19 showed a statistically significant 85% reduction of blood glucose excursion over the first 2-hours post-meal vs. Humalog (p<0.0001). While Adocia’s first BioChaperone Pramlintide Insulin (7.5 U human insulin/45 µg pramlintide) showed a 97% reduction in the same outcome vs. Humalog in September 2018, the company has prioritized ADO09 to progress in the pipeline because of its faster than expected development plan. In their 1Q19 statement, Adocia mentioned that a 3-week phase 1/2 trial was deferred to begin in 2H19 from a projected 2Q19 start time slated when results were initially released.

2. BioChaperone Lispro Studies Starting in China, No Reference on Status in US/EU; No Update on BC Combo, iLet Closed-Loop, or Obesity Pipeline

No mention was made of BC Lispro’s phase 2 bridging studies after a delay was announced in 1Q19. However, Adocia and Tonghua Dongbao (THDB) are currently working on qualification requirements to start phase 3 trials in China and other territories. Originally, a phase 2 bridging study of ultra-rapid-acting BC Lispro was expected to begin in 2Q19 to prepare for phase 3 filing in the US/EU in 4Q19. This study to confirm the manufacturing quality of active pharmaceutical ingredients (APIs) was further delayed to 3Q19 in 1Q19. Adocia’s 1H19 report gave no mention on the current status of this phase 2 trial in the US and EU, and instead, only offered updates on the beginnings of the phase 3 trial in China.

  • No update on BC Pramlintide Insulin (7.5 U human insulin/45 µg pramlintide) was given, as it appears that the candidate’s studies have halted to prioritize development of ADO09. Adocia’s 4Q18 update revealed that despite positive PD and safety results in phase 1, plans to begin a second, repeated administration trial for BC Pramlintide Insulin were pushed from 1Q19 to 2Q19. The only mention of the candidate in today’s update was to reaffirm messaging from 1Q19 that its development has been somewhat deprioritized in an effort to push development of ADO09 forward.

  • No update from THDB on their plans to bring BC Combo (75/25 basal insulin glargine/prandial insulin lispro) through a bridging study in China. While we initially learned in 1Q19 that THDB was planning to begin this study sometime in 2019 to enable use of data from previous BC Combo development, there was no mention of this venture in the 2Q19 report. The last that Adocia reported, the company was searching for partners for BC Combo in other markets with specific interest in China, where premix insulin makes up 65% of the overall insulin market at $5 billion (slide 18). 

  • After a phase 1 trial began in 1Q19, there were no further updates on BC Lispro in a closed-loop system (Beta Bionics’ iLet pump and algorithm and Dexcom CGM). According to the 1H19 report, the randomized, cross-over study will recruit up to 30 patients with type 1 to compare the PK/PD profiles of insulins lispro, aspart and BC Lispro in the iLet bionic pancreas, on an inter- and intrasubject basis. Just like in 1Q19, we were unable to find any such trial on ClinicalTrials.gov, so it’s still unclear whether this study has recruited enough participants to begin or how prioritized it is in Adocia’s pipeline.   

  • Adocia’s obesity pipeline was absent from the 1H19 report, giving no updates on BC Glucagon GLP-1 for obesity or BC Glucagon. As we understand it, BC Glucagon GLP-1 was set to enter phase 1 and BC Glucagon was set to enter phase 1/2 in 2H19 back in 1Q19, no updates were given on this front. As of its 3Q19 report, Adocia had originally planned to begin these studies in 1H19. 

3. Adocia Closes 2Q19 with ~$23 Million in Cash

As of June 30, Adocia held €20.7 million (~$23 million) in cash and cash equivalents. This is down €19.2 million (~$21.8 million) from January 1, 2019, during which Adocia had €39.8 million (~$45.2 million). This further continues a downward trend from €44 million in 3Q18 and €40 million in 4Q18. It is possible that Lilly’s payment of €11.6 million (~$13 million) and interest from the first arbitration, along with France’s research and tax credit payment (“Crédit d’Impôt Recherche;” €6.4 million, $7.2 million) will help buoy Adocia’s finances. However, the company is currently €8.1 million ($9.2 million) in debt, with a net increase of €1 million ($1.1 million) from December 31, 2018. Results of the second and final arbitration with Lilly will be key, as it could result in Adocia gaining ~$1.3 billion or losing ~$188 million to Lilly. A decision is expected soon in 3Q19.

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 yellow indicate 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 1b

  • 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; 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 Ursula Biba, Martin Kurian, and Kelly Close