Acetaminophen/Hydrocodone Bitartrate

One concern about the GLP-1 class of metabolic disorder drugs is that the weight patients lose includes muscle as well as fat. BioAge Labs wants to test whether its experimental medication, dosed alongside Eli Lilly’s weight management drug Zepbound, can preserve muscle mass. The startup recently closed $170 million to finance a mid-stage clinical trial. BioAge develops drugs that address aspects of human aging. Its lead drug candidate, azelaprag, is a small molecule designed to bind to and activate the apelin receptor, which regulates muscle metabolism, growth, and repair. This drug came from the labs of Amgen, which initially developed it for treating heart failure. Amgen’s Phase 1 tests showed the drug hit its target with a clean safety profile, BioAge CEO Kristen Fortney told MedCity News in a 2022 interview. But as a heart drug, the results were “not dramatic,” she said. Amgen elected to shelve the molecule. Richmond, California-based BioAge licensed it from the pharma giant in 2021, with the goal of testing it as a way of preserving muscle mass in elderly people. In BioAge’s Phase 1b study enrolling 21 participants age 65 and older, results showed the experimental drug led to statistically significant prevention of muscle atrophy relative to a placebo after 10 days of bed rest. The company planned to proceed to larger Phase 2 test enrolling intensive care unit patients, who can lose more than 15% of their muscle mass in just one week, according to published research. Last fall, BioAge announced the Phase 2 trial would go in a different direction. Instead of testing azelaprag in ICU patients, the trial will evaluate the drug alongside Eli Lilly’s Zepbound. The injectable drug, which activates the GLP-1 and GIP receptors, is an incretin mimetic, a type of drug that works by mimicking hormones found in the gut. The new clinical trial plan is based on preclinical research in obese mice. Results reported last year showed that treating the mice with both azelaprag and Lilly’s drug led to greater weight loss than what was achieved with the Lilly drug alone. The drug pairing also led to improvement in body composition and muscle function. Under a collaboration agreement, Lilly will supply Zepbound for BioAge’s trial, which will be run in collaboration with Chorus, a small independent clinical development organization within the pharma giant. BioAge adjusted its focus for azelaprag after the company’s technology uncovered new insight about the molecule. The BioAge discovery platform, built on analysis of human longevity data, identified a link between the apelin pathway activity and physical function during aging, Fortney said in an email. While the Phase 1b clinical trial led to results showing significant muscle and metabolic benefits in healthy elderly volunteers on bed rest, the molecule’s mechanism has multiple potential applications, Fortney said. “Obesity is the indication we are focusing on given the strong weight loss synergy we see preclinically with incretins,” she said. “This is an oral drug with the potential to increase weight loss quantity with a fully oral regimen, as well as to improve weight loss quality.” Fortney said BioAge will share more details on the design of the Phase 2 trial in the future, but the study will compare azelaprag (known at BioAge as BGE-105) in combination with Zepbound versus Zepbound alone. The primary endpoint will be weight loss. In addition, the company will monitor exploratory endpoints related to improvement of body composition—the balance of lean mass to fat mass. BioAge’s new capital will finance the planned Phase 2 test, which is on track to start in mid-2024. The Series D round was led by Sofinnova Investments. New investors joining the financing include Longitude Capital, RA Capital Management, Cormorant Asset Management, RTW Investments, SV Health Investors, OrbiMed Advisors, Sands Capital, Pivotal bioVenture Partners, Osage University Partners, Lilly Ventures, and Amgen Ventures. The latest round also included participation from earlier investor Andreessen Horowitz. Here’s a look at other recent life science industry financing activity: —Frontier Medicines, developer of targeted medicines for oncology and immunology, closed $80 million in financing to support its pipeline. The biotech’s most advanced program is FMC-376, which is in development for treating patients whose cancer is positive for KRAS G12C. This mutation was first drugged by Lumakras from Amgen and then Krazati from Mirati Therapeutics. Both drugs lock KRAS G12C protein in an inactive state. Frontier’s drug candidate is designed to block this cancer-driving protein in either its active or inactive states, potentially offering an option for patients who have not responded to the Amgen or Mirati drugs. In addition to supporting FMC-376, which recently dosed the first patient in a Phase 1/2 study, Frontier said the new capital will support other wholly owned programs in its pipeline. Deerfield Management Company and Droia Venture co-led the company’s Series C financing, which also included “significant participation” by Belgium-based drugmaker Galapagos. Frontier last raised money in 2021, an $88.5 million Series B round. —Firefly Bio revealed $94 million to finance R&D of degrader antibody conjugates, or DACs, which carry a protein degrader as the drug payload. In preclinical research, the biotech said its drugs led to “significant reduction of tumor volume at very low doses.” Firefly was incubated by Versant Ventures, which co-led the startup’s Series A financing with MPM BioImpact. —Roche, already an investor in liquid biopsy company Freenome, led an additional $254 million financing for the company. South San Francisco-based Freenome will apply the cash toward ongoing pivotal clinical trials evaluating its blood screening technology in colorectal cancer and lung cancer. The company is also conducting a study of its technology as a way to detect multiple cancers. Roche last invested in Freenome two years ago, a $290 million infusion that followed the company’s $300 million Series D financing. —Latigo Biotherapeutics launched with $135 million to finance clinical development of a non-opioid drug that blocks NaV1.8, a sodium channel associated with pain. It’s the same target addressed by a Vertex Pharmaceuticals drug candidate that recently posted data showing it met its main Phase 3 goal assessing pain relief compared to a placebo. But on a secondary goal of showing superiority to standard of care Vicodin, the Vertex drug came up short. Thousand Oaks, California-based Latigo claims its drug could be best in the class of NaV1.8 inhibitors with rapid onset, meaningful efficacy, and superior safety. It’s currently in Phase 1 testing. Latigo’s Series A financing was led by Westlake Village BioPartners, which incubated the startup. —Cancer immunotherapy developer NextPoint Therapeutics added $42.5 million to its Series B financing, bringing the round’s total to $122.5 million. The drugs of Cambridge, Massachusetts-based NextPoint target the HHLA2 pathway. NextPoint first announced its Series B round last year. —Sudo Biosciences expanded its Series B financing by $31 million, bringing the round’s total to $147 million. The new investors are Dementia Discovery Fund, Leaps by Bayer, and UPMC Enterprises. Carmel, Indiana-based Sudo emerged from stealth in 2022 to develop small molecule drugs that address TYK2, an autoimmune disease target first hit by the Bristol Myers Squibb drug Sotyktu. —Alys Pharmaceuticals launched with $100 million from Medicxi, the investment firm that formed the company. The preclinical biotech, which focuses on developing treatments for immune disorders of the skin, was formed by combining six Medicxi portfolio companies. Target indications include atopic dermatitis, vitiligo, psoriasis, and mastocytosis. —Antibody drug conjugate developer ProfoundBio closed $112 million in financing, which will be applied to clinical development of its pipeline. Lead program rinatbart sesuctecan, or Rina-S, targets folate receptor alpha, a validated cancer target. A pivotal Phase 1/2 study is underway in ovarian cancer. Ally Bridge Group led the Seattle-based biotech’s Series B round. ProfoundBio, whose management team brings experience from ADC specialist Seagen, emerged in 2021 backed by a $55 million Series A financing. —Areteia Therapeutics expanded its Series A round by $75 million with the addition of new investors Viking Global Investors and Marshall Wace. The Chapel Hill, North Carolina-based biotech’s Series A financing was announced at $350 million in 2022. Lead drug candidate dexpramipexole comes from the labs of Knopp Biosciences. Areteia is currently testing the molecule in three Phase 3 clinical trials enrolling patients with eosinophilic asthma, a severe form of asthma. —Basking Biosciences raised $55 million in a financing led by Arch Venture Partners. Columbus, Ohio-based Basking will use the capital to continue clinical development of BB-031, a potential treatment for acute ischemic stroke. The Basking drug is a reversible RNA aptamer designed to target von Willebrand factor, a clotting protein. BB-031 is engineered for both rapid onset and short duration of effect. Basking plans to start Phase 2 testing later this year. —Neurona Therapeutics, developer of regenerative medicines for neurological disorders, closed $120 million in financing. The San Francisco-based biotech makes cell therapies from human pluripotent stem cells, which have the ability to become almost any type of cell. Neurona will apply the capital toward ongoing Phase 1/2 testing of NRTX-1001, developed as a one-time treatment to silence epileptic seizures. Viking Global Investors and Cormorant Asset Management co-led Neurona’s Series E round. —Cour Pharmaceuticals has already out-licensed a celiac disease therapeutic candidate to Takeda Pharmaceuticals, which has advanced the nanoparticle-based therapy to Phase 2 testing. Chicago-based Cour wants to develop its own drug candidates and it raised $105 million to support programs in type 1 diabetes and myasthenia gravis. Lumira Ventures and Alpha Wave Ventures co-led the Series A financing, which included participation from three big pharma companies. —Eyconis, a new company formed with assets from Ascendis Pharma, launched with a $150 million financing commitment from an investor syndicate that includes Frazier Life Sciences, RA Capital Management, venBio, and HealthQuest Capital. Eyconis, which will operate from Redwood City, California, has ophthalmology assets developed from Ascendis’s Transcon platform. Ascendis, which has an equity stake in Eyconis, granted the biotech rights to develop and commercialize Transcon ophthalmology products globally. —Synnovation Therapeutics, founded and led by veterans of Incyte, launched with $102 million for small molecule drugs addressing validated cancer targets. Lead program SNV1521 is a PARP1 inhibitor that is highly selective to that target and also has the ability to penetrate into the central nervous system. The Wilmington, Delaware-based company is testing this molecule in a Phase 1 clinical trial. Third Rock Ventures led Synnovation’s Series A financing, which included participation from Nextech, Lilly Asia Ventures, Sirona Capital, and Cormorant Asset Management. Photo by Eli Lilly

Latigo Biosciences execs aren't worried about the likely first-in-class title for Vertex's pain med, saying there's plenty of room for both. A new pain-focused biotech is emerging this Valentine's Day—not to cure heartache, but pretty close. Latigo broke stealth cover today with $135 million to chase Vertex, the front runner in the effort to develop a new non-opioid pain option.  Latigo Biotherapeutics unveiled Wednesday with a lead nav1.8 inhibitor, LTG-001, currently being tested in healthy volunteers. If that target sounds familiar, it’s because Vertex is going after it as well with its own non-opioid treatment. VX-548 just beat placebo in a phase 3 trial in patients with acute pain but did not manage to best the standard of care, Vicodin. Vertex plans to file for FDA approval anyway this year and is seeking a broad label in moderate to severe acute pain.  Sean Harper, M.D., co-founding managing director of Westlake Village BioPartners, which founded and incubated Latigo beginning in 2020, said beating opioids is a "tough bar."  "I think a goal in an acute pain setting to beat that type of comparator handsomely … would have to be [an] aspiration," he said in an interview. With that said, Harper believes Latigo's molecule will differentiate from Vertex’s by mitigating off-target effects in the brain and by tackling chronic pain.  “We have every reason to believe that our nav1.8 inhibitor will be effective in both acute and chronic pain,” Harper said in an interview. “But obviously, that remains to be proven.” The asset is in a healthy volunteers study now, and executives hope to initiate a phase 2 study for patients with acute pain later this year.  Harper said some of the foundational science behind LTG-001 originated from the Lieber Institute for Brain Development in Baltimore but that preclinical work was done at labs in Thousand Oaks, California. The VC firm plucked homegrown talent for help, hiring many Amgen employees who left as part of the pharma’s neuroscience divestment in late 2019. The next molecule behind LTG-001 was developed completely in-house, Harper said, in addition to other discovery work.  Desmond Padhi, an operating partner at Westlake, will be the interim CEO while Neuron23 CEO Nancy Stagliano, Ph.D., has been called upon to chair the board. Although corralling investor interest is never easy, Stagliano acknowledged that Latigo has “hit this important catalyst at just the right time.”  “Once in a while, you get the timing to be perfect,” she said.  The inaugural financing was co-led by 5AM Ventures and Foresite Capital with participation from Corner Ventures. Padhi wouldn’t lay out how much of a runway the $135 million affords but expects it would allow the company to complete the ongoing phase 1 trial and a future phase 2 acute pain study while planning for the chronic pain study. He also said Latigo was planning to initiate a clinical trial for the second molecule in the “near future.”