Replies to post #250016 on Biotech Values

[DewDiligence]

PFE's qD Danuglipron warrants an entry in the "may surprise" group, IMO, even though we both consider the program high-risk.

[Mufaso]

UPDATED-List of ORAL Weight loss candidates.

12/15/23 Changes:

• Added Shionogi’s S-309309 which completed Ph 1 and is now in phase 2. It is a MGAT2 (Monoacylglycerol Acyltransferase). From Shionogi’s 2022 Investor Day, it appears that Shionogi’s plan is to use this drug in combination with a GLP1 analog. In Ph1 as a stand-alone treatment, it showed a weight loss of approximately 2% after 30 days of treatment. In combination with a GLP1 analog it showed a weight loss of approximately 4% after 30 days of treatment. It is claimed to have a promising safety profile.
  
• Added Danuglipron QD version as a “may surprise”
  
• Corrected an observation in the summary - Both Viking Therapeutics (VKTX) and Structure Therapeutics (GPCR) are the only small public companies with a new possible blockbuster oral obesity drug. Both are possible buyout candidates. (Previously I only noted just VKTX which is not accurate)

Here is an updated list of ORAL weight loss drugs currently in trials listed in possible commercial success tiers:

 
 		Most Interesting NME's	 
 	 
 Owner	Drug	        MOA		Comments 
 				 
 GPCR	GSBR-1290	GLP1		Structure Therapeutics -Significant weight loss in 28day Phase 1 (up to 4.9%) 
 VKTX	VK2809		GLP1/GIP	In phase 1- peptide 
 PFE	PF-06954522 	GLP-1		GLP1 for Type 2 Diabetes - just entered Ph1- very little info 
 AZN	ECC5004	        GLP-1		In Phase 1- small molecule GLP1- AZN paid 185mill + up to 1.8B milestones + royalties for compound. 
 Kallyope K757&K833	Hormone		New oral nutrient receptor agonists that stimulate the secretion of multiple appetite-suppressing satiety hormones 
 AMGN	Not Named	Undisclosed	Probably oral version of AMG 133 which activates GLP1 but inhibits GIP 
 RHHBY	CT996	        GLP1		In phase 1- small molecule.  From Carmot- Roche paid 2.7B for Carmot to acquire this Ph1 asset and 2 others 
 Shionogi S-309309      MGAT2	        In phase 2. Probably will be used in combination with a GLP1. Shionogi is listed in Tokyo as (4507.T) 
 				 
 				 
 		May surprise	 
 	 
 LLY	Orforglipron 	GLP1		In phase 3- No comment at last CC 
 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? 
 PFE	PF-06882961 	GLP1		Danuglipron QD formulation. In ph2b trial of the BID version, high rates of discontinuation & AE's caused PFE to not advance  
                                        the BID version. If QD version succeeds, it could be considered a shock rather than a surprise.  
  
 				 
 		Not going forward		 
 				 
 PFE	Lotiglipron 	GLP1		Discontinued due to elevated liver enzymes 
 PFE	PF-06882961 	GLP1		Danuglipron BID PH2b- high rates of discontinuation (greater than 50% across all doses) & AE's (up to 73% had nausea) 
  
 

Here are some observations:

• PFE is trying very hard in this arena.
  
• Kallyope is private but someone may buy them or strike a deal.
  
• Viking Therapeutics(VKTX) and Structure Therapeutics (GPCR) are the only small public companies with a NME having a potentially successful ORAL blockbuster. All other public companies are already "Big Pharma". Both are possible buyout candidates. Note that GPCR has completed phase 1 for their Oral drug but that Viking has yet to complete phase one for the oral form of VK2735. (only completed ph1 on the injectable form of VK2735)
  
• Structure Therapeutics (GPCR) market cap of $2.87B is primarily based on GSBR-1290 in Obesity
  
• 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.