I would say some of these interventions (the endogenously produced one like NMN) are more helpful when you are older not younger, they’re just ironically also more risky when older because the chances of cancer are higher. It’s possible that the body is deliberately downregulating production of these compounds with age in part to reduce the risk of cancer.
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My guess is that it has a lot to do with loss of immune function. The majority of cancers begin to appear during middle age. Same goes for infections. We slowly begin lose the capacity to deal with any negative consequence that our younger bodies could cope with. Homeostasis becomes harder and harder to maintain.
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Exactly. I think declining immunity is the main reason cancers become more common with age.
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A recent British show on longevity research in California, including some coverage of the BioAge Apelin drug:
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New presentation on their Phase 1B trial:
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Interview with BioAge VP:
and here:
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Here is Eric Morgan’s talk from last December’s Longevity Summit (slides of which were conveyd in the first post of this thread:
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This looks so promising. It’s just frustrating that biotech companies have to work around the fact that aging isn’t considered a disease. It just slows down the process of getting these drugs to market. Crossing fingers for this one. If it fulfills its promise it could be a blockbuster. Definitely worth looking out for the IPO if they go public.
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Longevity is going mainstream… BioAge just announced a $170 Million in Series D funding…
BioAge Announces $170 Million Oversubscribed Series D Financing to Accelerate Development of Obesity and Metabolic Disease Therapeutics
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Funding to advance Phase 2 clinical trials of azelaprag, an apelin receptor (APJ) agonist, in combination with Lilly’s Zepbound (tirzepatide) and therapeutic pipeline
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Azelaprag improves metabolic and muscle function and has potential as an oral drug to significantly increase weight loss and improve body composition in patients on GLP-1/incretin therapy
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James Healy, M.D., Ph.D., Managing Partner at Sofinnova Investments appointed as Chairman of the Board; Patrick Enright of Longitude Capital joins the Board of Directors of BioAge
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Thanks for posting. If this drug works out it could truly be a blockbuster. Just the positive benefits from preventing sarcopenia in patients who are bedridden or in the ICU would be huge. Older patients decline incredibly quickly if they break a hip and their survival rates are low. This would radically change those outcomes. Then there’s potential for it to be used to ‘keep people in shape’. I can see you being able to get in the best shape of your life and just stay that way. I’m sure there’s going to be some messy off target effects but if this pans out it’s going to be huge.
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And that is why I’m doing my own personal TRIIM experiment 
Nice. How long have you been doing it and how is it going?
I feel like a Telmisartan convert (‘evangelical’) as it is having a miraculous effect on visceral fat. Apparently it also significantly increases Apelin levels:
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I’ve been taking both Telmisartan and Amlodipine since 2005. No benefit for me in the weight area. Some people have different response levels to various interventions.
I do have 12 of the top 13 fat genes turned on though. So my weight has been an issue for as long as can remember.
Fortunately I’m a good responder to GLP1+GIP and very close to my ideal weight after starting it in July of 2023. There are quite a few good side effects with these drugs as well.
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In July 2023 we started Terzepatide for weight loss, then in August we added the next 2 compounds;
- GHRH - growth hormone releasing hormones, i.e. secretagogues (CJC1295 + Ipamoreln)
- Terzepatide to manage any potential glucose issue with the increase in GH from #1
- DHEA - a prohormone
So it’s “close” to the TRIIM protocol of
- Somatropin - synthetic GH
- Metformin
- DHEA
How is it going?
Overall I’d say very good. Been exposed to the many things little grandkids have and have not gotten sick in the past 8 months LoL! Compared to almost every visit catching one of their colds or whatever they have at the moment.
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RICHMOND, Calif.–(BUSINESS WIRE)-- BioAge Labs, Inc. (“BioAge”), a clinical-stage biotechnology company developing therapeutic candidates for metabolic diseases, such as obesity, by targeting the biology of aging, today announced preclinical data for its lead product candidate azelaprag, an orally available small molecule agonist of the apelin receptor APJ, in combination with incretin agonists for the treatment of obesity. The data were presented in a talk by BioAge’s Chief Medical Officer and EVP-Research Paul Rubin, MD, at the American Diabetes Association’s 84th Scientific Sessions. The conference, being held June 21–24 in Orlando, convenes more than 12,000 leading physicians, scientists, and health care professionals and features the latest scientific and therapeutic findings in diabetes.
In a mouse model of obesity, the addition of azelaprag to the GLP-1/GIP receptor agonist tirzepatide increased total weight loss to 39%, approximately double that of tirzepatide monotherapy, restoring body weight to the range observed in lean control mice. Furthermore, the combination restored body composition and muscle function to that of lean controls. Similar results were observed when azelaprag was combined with semaglutide, a GLP-1 receptor agonist. Importantly, the synergistic weight loss observed in animals on combination therapy was not due to a further decrease in food intake.
“We are highly encouraged by these preclinical data, which highlight the potential of azelaprag to significantly improve the weight loss and metabolic benefits of incretin therapy, the current standard of care for obesity,” said Kristen Fortney, Ph.D., CEO of BioAge. “Given its oral availability and favorable tolerability profile, we believe azelaprag is ideally suited for combination use with incretin drugs and could enable a new generation of patient-friendly, all-oral obesity regimens that could rival or even surpass the efficacy of injectables while also promoting healthy body composition.”
Azelaprag is a potential first-in-class oral agonist of the apelin receptor APJ. Apelin is an exercise-induced signaling molecule (exerkine) that acts on APJ to mediate many of the metabolic benefits of physical activity. In a Phase 1b trial, azelaprag promoted muscle metabolism and prevented muscle atrophy in healthy older volunteers on bed rest (link). The study also showed that azelaprag shifted circulating protein biomarkers in a manner consistent with its function as an exercise mimetic, increasing predicted resting energy expenditure and cardiorespiratory fitness.
BioAge plans to initiate a Phase 2 trial in mid-2024 evaluating azelaprag in combination with tirzepatide (Zepbound®) in older adults with obesity (link). The study is being conducted in collaboration with Eli Lilly and Company, which is providing tirzepatide, and Lilly’s Chorus clinical development organization, which is advising on trial design and execution.
Presentation Details:
Title: Apelin Receptor Agonist Azelaprag Increases Weight Loss in Diet-Induced Obese Mice on Incretin Agonists and Restores Body Composition and Muscle Function to that of Lean Controls
Abstract number: 118-OR
Session: Beyond Glucose and Weight Reduction—Additional Effects of Incretin-Based Therapies
Date/time: Friday, June 21, 2024, 4:15 – 4:30 PM
Presenter: Paul Rubin, MD, Chief Medical Officer and EVP-Research, BioAge Labs
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Azelaprag - Cas No. 2049980-18-7
Azelaprag (AMG 986) is an effective small-molecule apelin receptor agonist. .
Azelaprag, also known as AMG986, is a novel apelin receptor (APJ) agonist that improves cardiac contractility in animal models without adversely impacting hemodynamics. AMG 986 activate the APJ receptor in a manner similar to the endogenous ligands. AMG 986 inhibited forskolin-stimulated cAMP production and promoted Gα protein activation. AMG 986 is well tolerated, causing no adverse effects in nonclinical toxicology models.
One of my suppliers asked me if I’d be interested in a sample. I’d consider it
A bit more information from 2020
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Turns out this is quite an expensive drug for now. Have not looked at dose to see if it becomes cost effective. $8k per gram but if the dose is in the micro grams it “could” be cost effective $8 per mcg x ?? . Always cheaper by the kilo
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