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Antibe Therapeutics Inc(Pre-Merger) ATBPF

Antibe Therapeutics Inc. is a clinical-stage biotechnology company. The Company is leveraging its hydrogen sulfide (H2S) platform to develop therapies to target inflammation arising from a range of medical conditions. The Company’s pipeline includes assets that seek to overcome the gastrointestinal ulcers and bleeding associated with nonsteroidal anti-inflammatory drugs (NSAIDs). Its lead drug, otenaproxesul, is in clinical development as an alternative to opioids and NSAIDs for acute pain. Its second pipeline drug, ATB-352, is being developed for a specialized pain indication. The Company also focuses on inflammatory bowel disease (IBD). Otenaproxesul combines a moiety that releases hydrogen sulfide with naproxen, a non-steroidal, anti-inflammatory drug. ATB-352 is an H2S-releasing derivative of ketoprofen, a potent NSAID commonly prescribed for acute pain. Its IBD candidates are being designed to maintain the efficacy, safety, and pharmacokinetic properties of ATB-429.


GREY:ATBPF - Post by User

Post by mstrmndson Apr 13, 2024 7:26pm
401 Views
Post# 35987818

FDA Concerns

FDA Concerns1) Safety Data Clarification

The actual exposure based on the new Otenaproxesul formulation from the most recent PK/PD data is expected to be lower than prior conservative estimates because:

1) the new formulation has less impurities 
2) the new formulation has enhanced bioavailability
3) dose-dependent pharmacokinetics including excretion data allows the study dose to be below the threshold to trigger LTE based on conservative estimates
4) self-limiting LTE in the 1-2x range is subclinical and non-worrisome clinically (should be stratified and categorized as minor AE) consistent with other NSAIDS
5) self-limiting LTE (minor AE) in approximately 1/20 study participants is expected since the NSAID is derived from Naproxen

For all intensive purposes Otenaproxesul is an NSAID and should have a comparable exposure profile to other NSAIDs with less clinically-relelvant risks (major AE)

2) DILIsym Assumptions Data

This is straightforward and justification for assumptions will be provided.  Some of these assumptions may be inherent to DILIsym and are known limitations of modeling.  Antibe cannnot be held at fault for this.  Independent of the modelling assumptions, Antibe has completed the DILIsym modelling to provide additional non-clinical support for safety to alleviate the FDA's concerns.  DILIsym was not mandatory and modelling should not obstruct the clinical trial when sufficient in vivo data supports safety.  

The US FDA is disregarding 1) additional safety due to ulcer (mucosal) healing properties 2) non-addictive non-opioid analgesic properties that renders Otenaproxesul for acute indications actually much safer than existing pain meds or NSAIDs that clinically manifest with life-threatening GI complications.  It's a trade-off but 100/100 people would take a risk of 1/20 minor subclinical LTE like other NSAIDs (even alcohol binges) than ulcers, pain and GI bleeding.

I'm not worried about the FDA and neither should informed shareholders. 

GLTA





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