Memorandum

AntriaBio obtains $10 million in private financing for clinical development of once-weekly basal insulin AB101 – April 11, 2014

Executive Highlights

  • AntriaBio Inc. recently secured $10 million in private financing for “general corporate purposes,” including the upcoming clinical development program for a PEGylated basal insulin (AB101) with the potential for once-weekly administration.
  • An instructive slide set on company website indicates that AntriaBio hopes to file an IND with the FDA in early 2015

The California-based biotechnology company AntrioBio Inc. recently announced that it had raised $10 million in private financing. AntriaBio’s key product in development is a PEGylated once-weekly basal insulin (AB101) for type 1 and type 2 diabetes that is gearing up to enter clinical testing. The company press release states that the new round of financing will go towards general corporate purposes, including AB101’s clinical trial program, about which we are eager to learn more. An instructive slide set on the company website states that the company hopes to file an IND with the FDA in early 2015. This is one of the first few once-weekly insulin molecules we have heard of (PhaseBio has a candidate in phase 1), making it a key candidate to watch. Company management appears relatively confident in the new formulation’s safety, but given the mix of excitement and concerns that have arisen with other PEGylated basal insulins (namely Lilly’s phase 3 peglispro, which has shown a weight benefit but possible adverse effects on liver enzymes and triglycerides), we will be closely watching the clinical data that emerges on AB101. Assessing the risk/benefit balance of a once-weekly insulin will be key. The inability for patients to titrate their basal insulin to respond to day-to-day variation in diet and activity could be an issue for many. However, fewer injections is always a win – AntriaBio believes that once-weekly dosing will improve adherence to treatment compared to currently marketed once-daily basal insulins (including Sanofi’s Lantus and Novo Nordisk’s Levemir and Tresiba). Poor adherence, which is often driven by the pain and inconvenience of frequent injections, is often an issue for diabetes patients, making tools like AB101 that could reduce injection frequency valuable in that regard (assuming, of course, that the drug is safe). However, remembering doses is also an issue, and for some patients it might be easier to remember a once-daily over a once-weekly agent.

For background, AB101 consists of human recombinant insulin that is PEGylated (attached to a small molecular weight chain that allows the compound to be dissolved in both polar and non-polar solvents). This allows the PEGylated insulin to be encapsulated in biodegradable microspheres that slowly degrade to release insulin over time. In preclinical testing, the compound was able to achieve relatively stable insulin levels over a week without an early peak following once-weekly administration. AntriaBio acquired AB101 from PR Pharmaceuticals in early 2013 – by that point, PR had invested ~$100 million in the candidate although the investment was far lower as we understand it.

  • While once daily basal insulins were definitely seen as a major advance over their predecessors, it is not clear if once weekly dosing would represent as monumental of a leap. At last year’s EASD, Drs. Philip Home (Newcastle University, Newcastle Upon Tyne, UK) and Luigi Meneghini (University of Miami, Miami, FL) debated whether longer action is always better when it comes to basal insulins, touching upon the possibility of once-weekly options – see pages 3-6 of our EASD 2013 Insulin Report for our full coverage. Dr. Meneghini (who argued in favor of longer-acting insulins) stated his belief that there is a place for weekly insulin for some patients, as long as those patients’ basal insulin doses are fully optimized. Dr. Home noted that the day-to-day unpredictability of patients’ lives (in terms of diet and activity) could make titrating a once-weekly insulin difficult.
    • We are also not sure how much of a convenience benefit once-weekly vs. once-daily dosing would present in the minds of patients. At last year’s ADA, Dr. A. Brett Hauber (RTI Health Solutions, Durham, NC) presented the results of a discrete-choice experiment testing type 2 diabetes patient preferences for once-daily vs. once-weekly dosing for oral medications – although 67% of patients preferred a once-weekly option, the average patient was only willing to pay $5.86 more per month for a once-weekly vs. a once-daily pill (see pages 10-11 of our ADA 2013 Treatment Strategies Report. Of course, there are significant limitations in comparing preferences for an oral vs. injectable therapies (preference for less frequent administration would almost certainly be even higher with injectable agents, given the increased pain and inconvenience of injections). However, it is possible that some patients might find it easier to remember to dose once-daily compared to once-weekly, in addition to the day-to-day adjustability advantage that once-daily dosing provides.
  • Perhaps due to the uncertainty over the appeal and viability of once-weekly basal insulins, there are not very many players currently in the field. Novo Nordisk has a phase 1 candidate, LAI287 (NN1436), that has the potential for once-weekly dosing. It is an insulin analog (i.e., the primary amino acid sequence of the human insulin backbone has been modified) with an unspecified side chain attached that promotes stability. In June of last year, PhaseBio announced that it had initiated phase 1 testing of its once-weekly basal insulin Insumera (PE0139) – PhaseBio also has a once-weekly GLP-1 agonist Glymera (PB1023) that is currently in phase 2 testing.
  • Lilly has its own PEGylated insulin (peglispro) further along in clinical development (although it is targeted as a once-daily agent). Interestingly, that agent (a PEGylation of its rapid-acting insulin lispro) appears to be hepatoselective, which could lead to a weight benefit. However, investigators also found potentially worrying increases in liver enzymes and triglyceride levels with peglispro. If any of these positive or negative effects were due to PEGylation, they may come up in AB101’s clinical testing. However, AntriaBio’s overview page notes that AB101 utilizes a smaller PEG unit than other (unspecified) molecules, which could reduce any non-insulin effects.
  • Our questions include:
    • How will exercise impact blood glucose stability for patients on AB101?
    • How will the medicine be titrated?
    • What will the impact on adherence be?
    • Will clinical testing demonstrate either the positive or negative effects of hepatoselective action, due perhaps to AB101’s PEGylation?
    • At what stage might AntriaBio seek a partner for the continued development of AB101, if at all?

 

-- by Manu Venkat, Jessica Dong, and Kelly Close