UPDATED-List of ORAL Weight loss candidates.
03/27/2024 Changes:
- Separated Peptide/Large molecules from small molecules as a new category.
- Added NVO’s Amycretin which is a combination of GLP1 and amylin a single drug. (very similar to Cagrisema which is a combination of cagrilintide, a dual amylin and calcitonin receptor agonist, and semaglutide). Not much data released by NVO on tolerability. Surprisingly- not progressing to phase 2 very quickly.
- added NT-0796 from NodThera (Private) see #msg-173892107 which is a NLRP3 inflammasome inhibitor – targeted at Parkinson’s and now obese patients at risk of cardio. Probably will be studied in combo with a GLP1 at some point.
- Avg 8% wt. loss over a year. targeted at maintenance. Uses a combo of two off patent drugs Orlistat and Acarbose.
- Added/Updated PFE’s undisclosed Orals (one that is GLP1 based and another that is not) PFE commented on at Leerink
- Updated VK2735 to reflect phase 1 results
- Revised/added to some summary observations.
Most Interesting NME's as peptides/large molecules
Owner Drug MOA Comments
VKTX VK2809 GLP1/GIP Had exceptional tolerability in Ph1 while providing 3.3% weight loss vs placebo. Longer/larger trial may show improved benefits due to long half life.
NVO Amycretin GLP1/Amylin Great topline wt. loss in ph1 but... Not progressing until injectable form data out..very limited data released by NVO…small study. This is a combination of GLP1 and amylin a single drug.
Most Interesting NME's small molecules
Owner Drug MOA Comments
LLY Orforglipron GLP1 In ph2 the highest dose of 120mg got 3% weight loss at 4 wks, 8% at 8wks, and 13% at 36 weeks per GSBR comparison presentation
AZN ECC5004 GLP-1 In Phase 1- small molecule GLP1- AZN paid 185mill + up to 1.8B milestones + royalties for compound
PFE PF-06954522 GLP-1 GLP1 for Type 2 Diabetes - just entered Ph1- very little info
Kallyope K757&K833 Hormone new oral nutrient receptor agonists that stimulate the secretion of multiple appetite-suppressing satiety hormones
AMGN Not Named Undisclosed Unknown
GPCR GSBR-1290 GLP1 Structure Therapeutics -In larger ph2 study only showed 4% weight loss at 8weeks and look inferior to LLY's Orforglipron for both weight loss and T2D (Significant weight loss shown in 28day Phase 1 (up to 4.9%) was not borne out in larger ph2 study)
NodThera NT-0796 NLRP3 Not as effective as a GLP1 for weight loss but may be for those who can't tolerate GLP1 or has cardio issues
PFE Not Named "GLP based" Oral in Ph1- mentioned Leerink. M Dolsten said ->The second is another GLP-1 that has some different features also in the clinic and looks encouraging when it comes to PK and dose.
PFE Not Named "Non-GLP1" See #msg-173587109. Also- At Leerink M Dlosten said "But it's one of those mechanisms that being validated by biologicals from companies that are in that space,...the type of mechanism that you hear from Lilly and Novo. ... being the first company to make an oral version of it.
Empros EMP16 "Non GLP1" Avg 8% wt. loss over a year. targeted at maintenance. Uses a combo of two off patent drugs Orlistat and Acarbose.
May surprise
Owner Drug MOA Comments
PFE PF-06882961 GLP1 Danuglipron- Small Molecule- completed ph1 and in ph2b
NOVO Rybelsus GLP1 Semaglutide- approved for Diabetes only but used off label
TERN TERN-601 GLP1 Management discussing this drug in combination- not competitive standalone?
Not going forward
Owner Drug MOA Comments
PFE Lotiglipron GLP1 Discontinued due to elevated liver enzymes
Here are some observations:
- Amycretin is controversial in my view. They used a large quantity of drug to get a high top line weight loss but didn’t disclose much at all regarding tolerability. NVO is waiting for the phase one on the SubQ form of Amycretin to report out in 2025 before deciding what to do with this drug.The fact they are not advancing quickly to phase 2 is very telling IMO. Related messages include #msg-173999978 , #msg-173990476 , #msg-174001763
- PFE stated they at JPM Jan webcast that they are not going to do any “multi-billion acquisition obesity deals” but left partnership open
- Kallyope is private but someone may buy them or strike a deal. They are now exploring an IPO with JP Morgan.
- Viking Therapeutics(VKTX) and Structure Therapeutics (GPCR) are the only small public companies with a NME having a potentially successful ORAL blockbuster and are buyout candidates. All other public companies are already "Big Pharma". Note that GPCR’s phase 2 results lessened appeal.
- Structure Therapeutics (GPCR) market cap was reduced by 50% to $2B based upon ph2 for GSBR-1290
- Roche paid an eye opening $2.7B for Carmot Therapeutics and prevented Carmot from going public
Again, anyone with knowledge of new Oral weight loss drug candidates is encouraged to reply to this post.
