Kristen Fortney, PhD, BioAge Labs co-founder and CEO

Basking in the glow of a collaboration involving Eli Lilly’s diabetes/weight loss blockbuster tirzepatide, BioAge Labs has completed an oversubscribed $170 million Series D financing, the proceeds of which will support Phase II trials of a combination therapy.

The Phase II trials will combine BioAge’s lead pipeline candidate azelaprag (BGE-105), an oral apelin receptor (APJ) agonist, with incretin drugs designed to treat obesity—starting with tirzepatide, the glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) co-agonist indicated to treat adults with type 2 diabetes as Mounjaro®, as well as adults with obesity or who are overweight under the name Zepbound®.

Azelaprag is designed to work by binding APJ and activating apelin signaling in order to increase weight loss and improve body composition in combination with incretin drugs. Azelaprag mimics the activity of the exerkine apelin, a peptide that is released during exercise that improves metabolic and muscle function.

BioAge reasons that higher apelin activity is linked to longer lifespan and better physical function in later life—while azelaprag could significantly increase weight loss and improve body composition when combined with any incretin.

BioAge is prioritizing the azelaprag/tirzepatide combination after it promoted muscle metabolism, increased energy expenditure, and prevented muscle atrophy in healthy older volunteers at bedrest a Phase Ib trial (NCT06141889) in 2022. The combination therapy showed statistically significant improvement compared to placebo in muscle size, quality, and protein synthesis in volunteers ages 65 years and older during 10 days of bed rest, with no serious adverse effects.

“When you’re in bed rest, you see loss of muscle. You also see a reduction in energy expenditure, a reduction in predicted VO2 max [maximal oxygen consumption]. But these drugs [the combination therapy] have maintained all of those,” BioAge co-founder and CEO Kristen Fortney, PhD, told GEN Edge. “In the obesity context where you’re losing weight, where your body is changing, this will help preserve certain aspects of physiology and have beneficial effects.”

The Phase II studies of azelaprag and tirzepatide are expected to start in mid-2024. BioAge will be advised and assisted on all aspects of Phase II trial design and execution by Chorus, an operationally independent clinical development organization within Eli Lilly focused on working with biotechs to develop their pipeline candidates through clinical proof of concept.

“They’re actually going to be boots on the ground running the trials. And it’s great because we can benefit from Lilly’s past experience in the obesity space. They know all the best sites, all the best vendors, and can really take all that risk off the table for us,” Fortney said.

65M+ data points

Based in Richmond, CA, BioAge focuses on metabolic disease therapies that apply insights from human aging. The company says it has developed a platform consisting of more than 65 million data points collected from longitudinal samples, data, and health records of more than 10,000 patients over 45+ years. The platform uses multi-omics to measure 10,000-plus molecules per sample, as well as artificial intelligence (AI) to map longevity pathways and identify potential drug targets.

BioAge is among several pharma companies looking to develop oral muscle preserving drugs with obesity-focused partners.

Earlier this month, Regeneron Pharmaceuticals disclosed plans to launch a Phase II trial in mid-2024 that will assess semaglutide—the diabetes/obesity blockbuster marketed by Lilly’s metabolic drug arch-rival Novo Nordisk as Wegovy® (in obesity) and Ozempic® (in diabetes)—in combination with Regeneron’s trevogrumab, a fully human monoclonal antibody designed to inhibit myostatin.

The trial will evaluate the combination both with and without another Regeneron antibody candidate garetosmab, a fully human monoclonal antibody designed to bind and neutralize Activin A. Both garetosmab and trevogrumab were developed by Regeneron through its VelocImmune antibody platform.

And in 2022, Versanis Bio presented preclinical data reaffirming the potential of its lead candidate bimagrumab as both a monotherapy and co-administered with semaglutide or tirzepatide, as the combinations resulted in additive reduction of fat mass and gain of lean mass, predominantly muscle, in a diet-induced obesity model in mice.

“Murine bimagrumab triggered muscle hypertrophy and was able to reverse the muscle mass loss caused by incretin agonists,” a team of five Versanis researchers concluded.

Bimagrumab is a fully human monoclonal antibody designed to bind to activin receptor type 2A (ActRIIA) and type 2B (ActRIIB) on skeletal muscle. Last year, Lilly committed up to $1.925 billion in cash to acquire Versanis, which continues as a wholly owned subsidiary of the pharma giant.

BioAge licensed azelaprag from Amgen in 2021, back when the biotech giant called the drug AMG 986. BioAge agreed to pay Amgen an upfront payment as well as payments tied to achieving development and regulatory milestones—all undisclosed—plus royalties based on annual net sales.

Amgen also received shares in BioAge, which agreed to oversee all development, manufacturing, and commercialization of the drug, which BioAge named BGE-105 before renaming it azelaprag.

During preclinical studies, according to BioAge, azelaprag doubled the weight loss achieved on incretin drugs with improvements in body composition and muscle function.

Azelaprag may yet show beneficial results as a monotherapy, Fortney added: “There’s genetic data supporting that, but it will have much more profound effects as a combination.”

BioAge’s focus on longevity is an outgrowth of Fortney’s postdoctoral research at Stanford University about a decade ago, when she used bioinformatics to study the genetics of supercentenarians. Fortney co-founded BioAge in 2015 along with Eric Morgen, MD, the company’s COO.

A dozen new investors

BioAge’s Series D round, led by Sofinnova Investments, attracted a dozen new investors starting with Lilly’s venture capital arm, Lilly Ventures. Other new investors included Longitude Capital, RA Capital, Cormorant Asset Management, RTW Investments, SV Health Investors, OrbiMed Advisors, Sands Capital, Pivotal bioVenture Partners, Osage University Partners, and Amgen Ventures. They joined existing investors that included Andreessen Horowitz (a16z) Bio + Health.

In connection with the Series D financing, James Healy MD, PhD, managing partner at Sofinnova, has joined BioAge’s board as chairman while Patrick Enright, managing director at Longitude Capital, has joined as a director.

“The BioAge management team has laid very important scientific and clinical groundwork for the azelaprag program, and we look forward to working with the team to advance its clinical programs,” Healy stated.

The Series D financing raises to nearly $300 million BioAge’s total capital raised. The company’s previous financing was a $90 million Series C round completed in 2020, back when the company was working to develop an oral COVID-19 drug that reversed multiple aspects of immune aging.

That drug, BGE-175 (azapiprant), is no longer under development in BioAge’s pipeline. In addition to azelaprag, that pipeline includes two preclinical candidates—BGE-100, an NLRP3 inhibitor being developed as an oral neuroinflammation drug that is now in IND-enabling phase; and an undisclosed metabolic drug in the discovery phase.

BioAge says its latest Series D financing will extend its cash runway into at least late 2026. Asked when BioAge might consider going public, Fortney replied: “When it makes sense, right? There’s pros and cons, but biotech is expensive, especially when you’re in Phase II.”

Fortney said BioAge has grown to a staff of about 60—a workforce size that the company does not plan to grow dramatically.

“We have data scientists, we have people who work in vitro and in vivo, we have our clinicians. We’d like to stay lean,” Fortney said. “We don’t intend on bringing on more than maybe a couple of additional people. We’re pretty built out.”

“It’s still very much early days for the aging field, both from a basic science perspective, and also from a translational perspective. It’s still very much a new science, so there’s a lot of opportunity there. Most universities have tons of people working on oncology but maybe a couple of people working on aging, even though aging is really the biggest risk factor, right? So I think it’s very early days.”

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