A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Proof-of-Concept Study to Investigate Efficacy and Safety of Oral Azelaprag Plus Once Weekly Tirzepatide Compared with Tirzepatide Alone in Participants with Obesity Aged 55 Years and Over (STRIDES)

This study aims to find out how well a combination of oral azelaprag taken once a day (QD) or twice a day (BID), along with a weekly injection of tirzepatide, works for weight management in adults 55 years and older. The researchers are also looking at safety.
Estimated Study Length:
* with the optional prescreening, the study duration may be up to 48 weeks.
* the treatment duration will be 24 weeks followed by 12 weeks follow-up.
* the visit frequency will be every 2 weeks for the first 8 weeks of the treatment period and every 4 weeks thereafter.

Start Date27 Jun 2024

Sponsor / Collaborator

BioAge Labs, Inc.Startup

[+1]

NCT06141889

/ CompletedPhase 1

A Phase 1, Single-dose, Open-label, Randomized Crossover and Multiple-dose, Open-label Study to Evaluate the Pharmacokinetics and Safety of Azelaprag in Older Adult Healthy Volunteers

This study is a single-dose, open-label, randomized crossover and multiple-dose, open-label study to evaluate the PK of azelaprag in older adult healthy volunteers.

Start Date17 Nov 2023

Sponsor / Collaborator

BioAge Labs, Inc.Startup

NCT03318809

/ CompletedPhase 1

A Phase 1, Open-label, Single-dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AMG 986 Administered Orally to Healthy Volunteers and Subjects With Severely Impaired Renal Function

A study to assess the safety, tolerability, and pharmacokinetics of AMG 986 given orally as a single dose to healthy participants and participants with severely impaired kidney function.

Start Date12 Dec 2017

Sponsor / Collaborator

Amgen, Inc.

100 Clinical Results associated with Azelaprag

100 Translational Medicine associated with Azelaprag

100 Patents (Medical) associated with Azelaprag

Literatures (Medical) associated with Azelaprag

23 Aug 2024·ORGANIC LETTERS

Structural Elucidation and Absolute Stereochemistry for Pharma Compounds Using MicroED

Article

Author: Caille, Seb ; Walker, Shawn D. ; Mai, Huanghao ; Cee, Victor J. ; Nelson, Hosea M. ; Wurz, Ryan P. ; Rodriguez, Isabel Hernandez ; Smith, Austin G. ; Gostovic, Dan ; de Moraes, Lygia Silva ; Rodriguez, Jose A. ; Burch, Jessica E. ; Delgadillo, David A. ; Quasdorf, Kyle

Microcrystal electron diffraction (microED) is an emerging technique for rapid crystallographic analysis of small molecule micro- and nanocrystals. In this report, we evaluate the applicability of microED to pharmaceutical compounds through the analysis of 30 samples obtained from the process and medicinal chemistry groups at Amgen Inc. Using only 40 h of microscope time, 15 of 30 crystal structures were elucidated. From these crystal structures, all chiral compounds had the correct absolute stereochemistry assigned by dynamical refinement of continuous rotation electron diffraction data, confirming dynamical refinement as a promising tool for the absolute stereochemistry determination of pharmaceutically relevant compounds.

01 Aug 2023·Cardiovascular drugs and therapy

A First-in-Human Study of AMG 986, a Novel Apelin Receptor Agonist, in Healthy Subjects and Heart Failure Patients

Article

Author: Goldsmith, Steven ; Trivedi, Ashit ; Lepage, Serge ; Winkle, Peter ; Kazemi, Navid ; Hellawell, Jennifer ; Tsirtsonis, Kate ; Troughton, Richard ; Voors, Adriaan ; Hulot, Jean-Sebastien ; Donal, Erwan ; Koren, Michael J ; Neutel, Joel ; Kaufman, Allegra ; Abbasi, Siddique A

PURPOSE:

AMG 986 is a novel apelin receptor (APJ) agonist that improves cardiac contractility in animal models without adversely impacting hemodynamics. This phase 1b study evaluated the safety/tolerability, pharmacokinetics, and pharmacodynamics of AMG 986 in healthy subjects and patients with heart failure (HF).

METHODS:

Healthy adults (Parts A/B) and HF patients (Part C) aged 18-85 years were randomized 3:1 to single-dose oral/IV AMG 986 or placebo (Part A); multiple-dose oral/IV AMG 986 or placebo (Part B); or escalating-dose oral AMG 986 or placebo (Part C).

PRIMARY ENDPOINT:

treatment-emergent adverse events, laboratory values/vital signs/ECGs; others included AMG 986 pharmacokinetics, left ventricular (LV) function.

RESULTS:

Overall, 182 subjects were randomized (AMG 986/healthy: n = 116, placebo, n = 38; AMG 986/HF: n = 20, placebo, n = 8). AMG 986 had acceptable safety profile; no clinically significant dose-related impact on safety parameters up to 650 mg/day was observed. AMG 986 exposures increased nonlinearly with increasing doses; minimal accumulation was observed. In HF with reduced ejection fraction patients, there were numerical increases in percent changes from baseline in LV ejection fraction and stroke volume by volumetric assessment with AMG 986 vs placebo (stroke volume increase not recapitulated by Doppler).

CONCLUSIONS:

In healthy subjects and HF patients, short-term AMG 986 treatment was well tolerated. Consistent with this observation, clinically meaningful pharmacodynamic effects in HF patients were not observed. Changes in ejection fraction and stroke volume in HF patients suggest additional studies may be needed to better define the clinical utility and optimal dosing for this molecule.

TRIAL REGISTRATION NUMBER:

ClinicalTrials.gov NCT03276728.

DATE OF REGISTRATION:

September 8, 2017.

01 Jul 2022·Clinical pharmacology in drug development

A Phase 1, Open‐Label Study to Evaluate the Effect of Food and Concomitant Itraconazole Administration on the Pharmacokinetics of AMG 986 in Healthy Subjects

Article

Author: Mather, Omar ; Hutton, Shauna ; Vega, Silvia ; Trivedi, Ashit ; Lee, Edward ; Hellawell, Jennifer

Abstract:

This phase 1, open‐label study evaluated the effect of food and administration of the cytochrome P450 3A4 and P‐glycoprotein inhibitor itraconazole (ITZ) on the pharmacokinetics of AMG 986. In cohort 1, 12 healthy subjects received a single oral dose of AMG 986 200 mg ± food on days 1 and 10. In cohort 2, 15 healthy subjects received oral ITZ 200 mg once daily on days 8 to 15 and a single oral dose of AMG 986 10 mg on days 1 and 11. The geometric least squares mean ratios of fed/fasted for AMG 986 maximum observed concentration (Cmax) and area under the plasma concentration–time curve from time 0 to infinity (AUCinf) were 0.76 (90%CI, 0.61‐0.95) and 1.07 (90%CI, 0.94‐1.22), respectively. The geometric least squares mean ratios of AMG 986 10 mg plus ITZ 200 mg/AMG 986 10 mg alone for AMG 986 Cmax and AUCinf were 1.36 (90%CI, 1.25‐1.48) and 5.13 (90%CI, 4.71‐5.59), respectively. Overall, 3 subjects experienced mild treatment‐related adverse events; there were no serious or fatal adverse events. In conclusion, food had no apparent effect on the exposure of AMG 986 200 mg; therefore, food restrictions are not required. Potent cytochrome P450 3A4 and/or P‐glycoprotein inhibitors may warrant AMG 986 dose reduction and should be coadministered with caution in patients with heart failure treated with AMG 986.

News (Medical) associated with Azelaprag

28 Jan 2025

·www.fiercebiotech.com

BioAge axes obesity asset over liver toxicity, pivots to preclinical prospects

BioAge Labs has picked brain-penetrant molecule BGE-102 as its development candidate. \n BioAge Labs has given up on its lead obesity candidate. Weeks after stopping a trial in response to phase 2 data, the biotech has jettisoned the molecule and shifted its focus to a preclinical neuroinflammation prospect.California-based BioAge raised around $200 million in an IPO in September and swiftly reminded public investors that biotechs are risky bets. Two months after going public, BioAge stopped a phase 2 trial of its oral apelin receptor agonist azelaprag. Investors fled, but the biotech left the door open, noting that it remained encouraged by preclinical and early-phase data and vowing to share updated plans in 2025.BioAge closed the door on azelaprag Tuesday, explaining that the elevated liver enzymes seen in some patients without clear dose dependence had persuaded it to call time on the program. The biotech has structurally distinct molecules in its pipeline and aims to pick a follow-up candidate this year.With the apelin program bouncing back to preclinical, BioAge’s NLRP3 inhibitor has become the biotech’s most advanced prospect. Management has picked brain-penetrant molecule BGE-102 as its development candidate and is running studies to support a filing to test the asset in humans. BioAge expects to post phase 1 single-ascending dose data on the candidate this year. NLRP3 was a hot target as the 2010s drew to a close, when Bristol Myers Squibb, Novartis and Roche—both through its mothership and Genentech subsidiary—all acquired assets. None of the deals has led to an approved NLRP3 inhibitor.BioAge is initially focused on molecules that are active in the central nervous system. NodThera, Ventyx Biosciences, Roche and Ventus Therapeutics have all worked on similar molecules, but BioAge is bullish, with CEO Kristen Fortney, Ph.D., using a Citi event last month to claim the candidates are “an order of magnitude more potent than the competition.”The biotech’s focus on the neuroinflammatory uses of NLRP3 inhibition is built on longevity data linking the protein to accelerated cognitive aging and shorter life spans. BioAge also has evidence that inhibiting the protein could suppress appetite, suggesting there is scope to expand into obesity.Investors appeared to have priced in the pivot away from azelaprag, with the stock opening flat Tuesday. BioAge’s stock has fallen more than 75% since last year’s IPO, but the biotech has the money to write a second act—the company\'s cash runway extends beyond 2029. BioAge disclosed a collaboration with Lilly ExploR&D to discover two antibodies against metabolic aging targets identified by the biotech.

IPOPhase 2Phase 1

28 Jan 2025

·www.globenewswire.com

BioAge Labs Announces Company Updates on APJ, NLRP3, and Platform Programs

Advancement of next-generation APJ agonists with discontinuation of azelaprag Nomination of NLRP3 inhibitor BGE-102 as a development candidate, with initial Ph1 clinical data anticipated by end of 2025 Expansion of discovery efforts based on insights from BioAge’s platform, including a target identification collaboration with Novartis and a newly announced antibody therapeutics development collaboration with Lilly ExploR&D RICHMOND, Calif., Jan. 28, 2025 (GLOBE NEWSWIRE) -- BioAge Labs, Inc. ("BioAge", “the Company”), a clinical-stage biopharmaceutical company developing therapeutic product candidates for metabolic diseases by targeting the biology of human aging, today announced company updates for its programs and platform. • Advancement of next-generation APJ agonists with discontinuation of azelaprag BioAge has terminated development of azelaprag, an orally available small molecule agonist of APJ, for obesity and other chronic diseases. The decision follows observations of liver transaminitis without clinically significant symptoms, and without clear dose dependence, in some patients in the azelaprag arms of the STRIDES Phase 2 clinical trial for obesity (link). BioAge is developing structurally distinct APJ agonists in its pipeline, with the goal of nominating a development candidate by the end of 2025. • Nomination of NLRP3 inhibitor BGE-102 as a development candidate, with initial Ph1 clinical data anticipated by end of 2025 BioAge is developing its novel, proprietary class of NLRP3 inhibitors, which have distinctive structural and biological properties and include molecules that penetrate the blood–brain barrier, for diseases associated with neuroinflammation. The Company has nominated a member of this class, the orally available, small-molecule brain-penetrant NLRP3 inhibitor BGE-102, as a development candidate. The structurally novel drug has potential best-in-class features, including high potency and high brain penetration, an important attribute for a compound that could be used for treatment of neuroinflammation linked to conditions such as obesity. IND-enabling experiments for BGE-102 are currently underway, and Phase 1 SAD data are anticipated by the end of 2025. • Expansion of discovery efforts based on novel insights from BioAge’s platform, including collaborations with Novartis and Lilly BioAge continues to leverage its discovery platform, which analyzes longitudinal human aging data to reveal the key molecular drivers of healthy aging to discover novel targets and molecules, via internal development programs and ongoing strategic collaborations. In December, BioAge announced a multi-year research collaboration with Novartis to identify and validate novel therapeutic targets at the intersection of aging biology and exercise, combining BioAge's longitudinal human aging datasets with Novartis expertise in exercise biology. Under the terms of the agreement, BioAge will receive up to $20 million in upfront payments and research funding, plus up to $530 million in future long-term research, development, and commercial milestones (link). BioAge has also entered a strategic collaboration with Lilly ExploR&D (part of Lilly Catalyze360) to discover two therapeutic antibodies that address novel metabolic aging targets identified by BioAge's discovery platform. • Financial update As of September 30, 2024, BioAge had approximately $334.5 million in cash and cash equivalents. This amount is not inclusive of the additional $27.6 million net fees from the exercise of the IPO’s greenshoe option on October 1, 2024. Existing cash and cash equivalents extend cash runway beyond 2029. About BioAge Labs, Inc. BioAge is a clinical-stage biopharmaceutical company developing therapeutic product candidates for metabolic diseases by targeting the biology of human aging. The company’s pipeline includes novel, orally available, brain-penetrant small-molecule NLRP3 inhibitors to treat metabolic diseases and conditions driven by neuroinflammation, as well as novel, structurally differentiated APJ agonists for metabolic disorders. BioAge’s additional preclinical programs, which leverage insights from the Company’s proprietary discovery platform built on human longevity data, address key pathways involved in metabolic aging. Forward-looking statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements." These statements include, but are not limited to, statements relating to anticipated preclinical and clinical development activities, timing of announcements of clinical results, trial initiation, and regulatory filings, potential benefits of the Company’s other product candidates and platform, the potential and timing of future milestone payments under the agreement with Novartis, and the current expected cash runway. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: BioAge’s ability to advance its product candidates, the timing and results of preclinical and clinical trials, the Company’s ability to fund development activities and achieve development goals, the Company’s ability to protect intellectual property, the Company’s commercial collaborations with third parties, the potential impact of global business or macroeconomic conditions, and the sufficiency of BioAge’s cash, cash equivalents and investments to fund its operations, and other factors discussed under the heading "Risk Factors" section of the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024 and other documents BioAge files from time to time with the Securities and Exchange Commission. Any forward-looking statements contained in this press release are based on the current expectations of BioAge's management team and speak only as of the date hereof, and BioAge specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. ContactsPR: Chris Patil, media@bioagelabs.com IR: Dov Goldstein, ir@bioagelabs.com Partnering: partnering@bioagelabs.com Web: https://bioagelabs.com

License out/inPhase 2

28 Jan 2025

·endpts.com

Akero, 89bio disclose public offerings; BioAge drops Phase 2 obesity drug

Plus, news about Vigonvita Life Sciences and Lutris Pharma: For MASH developers, a race for cash: Akero Therapeutics aims to raise $300 million in an offering that was announced the same day it disclosed new mid-stage data for the drug it’s developing to treat severe forms of the liver disease. 89bio, which has a MASH candidate in Phase 3, also announced an offering on Monday, saying it plans to sell shares to raise $250 million. — Jaimy Lee BioAge officially drops Phase 2 obesity drug: The Richmond, CA-based biotech terminated development of azelaprag, the oral small molecule APJ agonist licensed from Amgen, after liver concerns forced it to stop a trial last month. The biotech has other APJ agonists in preclinical development, and it plans to soon send an NLRP3 inhibitor into the clinic. It anticipates having early Phase 1 single-ascending dose data by year’s end. The startup also disclosed a Lilly ExploR&D collaboration for two antibodies for “metabolic aging targets” found using BioAge’s discovery platform. Terms of the deal were not disclosed. — Kyle LaHucik Another HKEX IPO filing: A Chinese biopharma called Vigonvita Life Sciences has filed to go public on the Hong Kong Stock Exchange. The Suzhou-based drug developer has an approved Covid-19 treatment in China and Uzbekistan, plus a pipeline of candidates for RSV, depression, epilepsy, schizophrenia and other indications. — Kyle LaHucik Israeli biotech gets $30M: Lutris Pharma said the funding will help it test a topical gel that aims to reduce EGFRi-induced rashes caused by certain cancer drugs. Columbus Venture Partners, Pontifax Venture Capital, Peregrine Ventures and aMoon Fund backed the Tel Aviv-based startup, which expects to have topline Phase 2 results in the first half of this year. — Kyle LaHucik

Phase 2Phase 1IPOPhase 3

100 Deals associated with Azelaprag

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Obesity	Phase 2	United States	BioAge Labs, Inc.Startup	27 Jun 2024
Muscular Atrophy	Phase 2	-	BioAge Labs, Inc.Startup	-
Heart failure with normal ejection fraction	Phase 1	United States	Amgen, Inc.	12 Aug 2016
Heart failure with normal ejection fraction	Phase 1	Australia	Amgen, Inc.	12 Aug 2016
Heart failure with normal ejection fraction	Phase 1	Canada	Amgen, Inc.	12 Aug 2016
Heart failure with normal ejection fraction	Phase 1	France	Amgen, Inc.	12 Aug 2016
Heart failure with normal ejection fraction	Phase 1	Germany	Amgen, Inc.	12 Aug 2016
Heart failure with normal ejection fraction	Phase 1	Netherlands	Amgen, Inc.	12 Aug 2016
Heart failure with normal ejection fraction	Phase 1	New Zealand	Amgen, Inc.	12 Aug 2016
Heart failure with normal ejection fraction	Phase 1	Poland	Amgen, Inc.	12 Aug 2016

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


BusinessWire Manual	Phase 1	Muscular Atrophy	21	BGE-105	hczdgxldrp(vggrbipwmb) = kflkwubdkq leryegtpkk (vdkgnhulat ) View more	Positive	05 Dec 2022
				Placebo	qiptzzgvkd(ucmgotwcal) = xbprihvlfk ursanuvaos (uiyqucovad )
NCT03276728 (CTgov)	Phase 1	Heart failure with normal ejection fraction \| Heart Failure \| Heart failure with reduced ejection fraction	182	Placebo PO (Part C: HFrEF Placebo)	hzbzkpqfey = ipagwqoeej gehluxmzlg (gvhmkvtmkd, eivsyakldo - xzaqqyepao) View more	-	08 Aug 2022
				Placebo PO (Part C: HFpEF Placebo)	hzbzkpqfey = irmbiakudg gehluxmzlg (gvhmkvtmkd, atwvbeujbt - mwilurkafv) View more
NCT03318809 (CTgov)	Phase 1	Heart Failure	12	AMG 986 (Group 1: Severely Renal Impaired Participants)	lssqvklyys(amplhpsshc) = wafyzxeigu vpvpxugtze (eoyipaijgk, 33.6) View more	-	27 Jan 2021
				AMG 986 (Group 2: Healthy Participants)	lssqvklyys(amplhpsshc) = zfytydxdms vpvpxugtze (eoyipaijgk, 70.0) View more

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