Replies to post #250372 on Biotech Values

[Mufaso]

Kallyope is exploring an IPO with JPMorgan:

Oral Weight-Loss Drug Developer Kallyope Exploring IPO
https://finance.yahoo.com/news/oral-weight-loss-drug-developer-194613314.html

Kallyope has two oral medicines in mid-stage clinical trials as treatments for both obesity and type 2 diabetes.

Kallyope, founded by three researchers at Columbia University, was valued at $1.14 billion after its last round of venture funding in 2022, according to Pitchbook. Its investors include Bill Gates and Abu Dhabi wealth fund Mubadala Investment Co. Franz Humer...

There are many well know Hormones having an impact on appetite and satiety. Kallyope is targeting with K-757 and K-833. Kallyope has disclosed that they target cholecystokinin (CCK) and Peptide YY (PYY).

I will be very interested in the prospectus if Kallyope makes it to market. I wouldn't be surprised if the current value of the company was well over the $1.14 billion it was valued at in 2022. Carmot was in the process of doing and IPO and never made it because Roche bought them.

[DewDiligence]

NodThera Ltd—(private)—has an oral weight-loss drug called NT-0796
in phase-1/2 (the same drug NodThera is developing Parkinson’s):

https://www.clinicaltrials.gov/study/NCT06129409

Related links:
https://www.nodthera.com/pipeline/

https://www.fiercebiotech.com/research/nodtheras-clinical-nlrp3-inhibitor-almost-matches-wegovy-weight-loss-mice-bonus-heart

https://jpet.aspetjournals.org/content/jpet/early/2024/02/08/jpet.123.002013.full.pdf

[DewDiligence]

Empros Pharma—(private)—oral agent—>8% mean_weight_loss_in_24w_phase-2b_ trial_of_330_patients:

https://www.linkedin.com/posts/empros-pharma_empros-pharma-releases-topline-data-on-weight-activity-7170768008418582528-RckP

The oral agent is a fixed-dose combination of two approved generic drugs: the lipase inhibitor, orlistat; and the glucosidase/amylase inhibitor, acarbose.

[DewDiligence]

PFE has an oral *non*-GLP-1 obesity candidate that has completed phase-1 and has same (undisclosed) target as injectable candidates in clinical trials from other companies, according to PFE’s CSO on today’s Leerink webcast.

[DewDiligence]

Re: Oral weight-loss drug candidates

The implied premise of the excellent compilation I’m replying to is that all oral weight-loss drugs are competing against one another; however, I think it is more constructive to consider oral peptide weight-loss drugs and oral small-molecule weight-loss drugs as distinct categories.

Oral peptide drugs have poor bioavailability, and this has several knock-on effects, all of which are negative:

• High inter-patient variability in exposure to the active agent, which makes dosing tricky;

• Strict fasting requirements (so the GI system is lulled into not treating the peptides as food);

• Large doses (to overcome low bioavailability) that drive up the cost of goods.

Bottom line: I expect that oral small-molecule weight-loss drugs will be a blockbuster category, but oral peptide weight-loss drugs will be marginal players, at best.

[Mufaso]

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.