An Open-Label Long-Term Phase III Extension Study to Assess the Long-Term Safety and Tolerability of Dexpramipexole in Participants With Severe Eosinophilic Asthma

The goal of this clinical trial] is to evaluate the long term safety of dexpramipexole treatment in participants with severe asthma, aged ≥12 years, on Global Initiative for Asthma (GINA) 2021 [GINA, 2021] Step 4 or 5 therapy and who completed either of the Phase III studies EXHALE-2 or EXHALE-3.

开始日期2024-05-08

申办/合作机构

Areteia Therapeutics, Inc.初创企业

NCT05813288 / Recruiting临床3期

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Dexpramipexole Administered Orally for 52 Weeks in Participants With Severe Eosinophilic Asthma

The objective of this clinical study is to investigate the safety, tolerability, and efficacy of dexpramipexole in participants with inadequately controlled severe eosinophilic asthma.

开始日期2023-03-27

申办/合作机构

Areteia Therapeutics, Inc.初创企业

NCT05748600 / Recruiting临床3期

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Dexpramipexole Administered Orally for 24 Weeks in Participants With Eosinophilic Asthma

The purpose of this study is to evaluate dexpramipexole as an add-on oral therapy in participants with inadequately controlled eosinophilic asthma to evaluate improvements in lung function, asthma control, and quality of life. In addition, the study will further evaluate the safety and tolerability of dexpramipexole in participants with eosinophilic asthma.

开始日期2023-01-30

申办/合作机构

Areteia Therapeutics, Inc.初创企业

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项与右旋普拉克索相关的文献（医药）

2024-02-01·Current opinion in allergy and clinical immunology

Chronic rhinosinusitis with nasal polyps: eosinophils versus B lymphocytes in disease pathogenesis

Review

作者: James, Louisa K ; Kariyawasam, Harsha H

Purpose of review:

To highlight the current evidence that supports the view that eosinophils may not drive disease in chronic rhinosinusitis with nasal polyps (CRSwNP) and the emerging evidence for B cells as an important player in this disease.

Recent findings:

Eosinophil depletion studies in CRSwNP do not fully support a critical role for eosinophils in CRSwNP. Almost complete eosinophil depletion with dexpramipexole had no impact on polyp size reduction or clinical improvement. Anti-interleukin (IL)-5 and IL-5Rα inhibition were more effective though with less clinical impact when compared to anti-immunoglobulin E (IgE) or IL-4Rα inhibition strategies. As IL-5Rα is also expressed on CRSwNP derived IgE+ and IgG4+ plasma cells to the same extent as eosinophils, improvements in CRSwNP with IL-5 inhibition may suggest a role for B cells over eosinophils in CRSwNP. We review both eosinophils and B cells in the context of CRSwNP and highlight the current evidence that supports an emerging role for B cells.

Summary:

Despite many aspects of immunopathology in CRSwNP explainable by B cell dysfunction, B cells have so far been ignored in CRSwNP. Further work is needed, as targeting B cells may offer an exciting new therapeutic option in the future.

2023-11-01·The Journal of allergy and clinical immunology

Refashioning dexpramipexole: A new horizon in eosinophilic asthma?

Communications

作者: Cusack, Ruth P ; Sulaiman, Ibrahim ; Gauvreau, Gail M

2023-11-01·The Journal of allergy and clinical immunology

Safety and Efficacy of Dexpramipexole in Eosinophilic Asthma (EXHALE): A randomized controlled trial

Article

作者: Mather, James L ; Panettieri, Reynold A ; Schwartz, Justin T ; Wenzel, Sally E ; Jacobsen, Elizabeth A ; Ghearing, Natasha ; Bozik, Michael E ; Siddiqui, Salman ; Ochkur, Sergei I ; Archibald, Donald G ; Prussin, Calman ; Killingsworth, Randall ; Dworetzky, Steven I ; Busse, William W

BACKGROUND:

There is a need for new and effective oral asthma therapies. Dexpramipexole, an oral eosinophil-lowering drug, has not previously been studied in asthma.

OBJECTIVE:

We sought to evaluate the safety and efficacy of dexpramipexole in lowering blood and airway eosinophilia in subjects with eosinophilic asthma.

METHODS:

We performed a randomized, double-blind, placebo-controlled proof-of-concept trial in adults with inadequately controlled moderate to severe asthma and blood absolute eosinophil count (AEC) greater than or equal to 300/μL. Subjects were randomly assigned (1:1:1:1) to dexpramipexole 37.5, 75, or 150 mg BID (twice-daily) or placebo. The primary end point was the relative change in AEC from baseline to week 12. Prebronchodilator FEV₁ week-12 change from baseline was a key secondary end point. Nasal eosinophil peroxidase was an exploratory end point.

RESULTS:

A total of 103 subjects were randomly assigned to dexpramipexole 37.5 mg BID (N = 22), 75 mg BID (N = 26), 150 mg BID (N = 28), or placebo (N = 27). Dexpramipexole significantly reduced placebo-corrected AEC week-12 ratio to baseline, in both the 150-mg BID (ratio, 0.23; 95% CI, 0.12-0.43; P < .0001) and the 75-mg BID (ratio, 0.34; 95% CI, 0.18-0.65; P = .0014) dose groups, corresponding to 77% and 66% reductions, respectively. Dexpramipexole reduced the exploratory end point of nasal eosinophil peroxidase week-12 ratio to baseline in the 150-mg BID (median, 0.11; P = .020) and the 75-mg BID (median, 0.17; P = .021) groups. Placebo-corrected FEV₁ increases were observed starting at week 4 (nonsignificant). Dexpramipexole displayed a favorable safety profile.

CONCLUSIONS:

Dexpramipexole demonstrated effective eosinophil lowering and was well tolerated. Additional larger clinical trials are needed to understand the clinical efficacy of dexpramipexole in asthma.

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2024-05-29

·FierceBiotech

Public-private collaboration aims to take ALS therapies beyond 'a shot in the dark'

The new program's forthcoming database will fill in the knowledge gaps by first compiling existing data from various entities. In 2015, after spending nearly four decades grinding his way up the ladder at one of the world’s most prolific construction equipment companies, Ed Rapp was nearing its apex. He had risen from humble beginnings in a town of fewer than 800 people to presiding over Caterpillar Inc.’s massive Resource Industries division. He was in the running to become CEO. Then the rug was pulled out from under him. Rapp was diagnosed with the incurable neurodegenerative disease amyotrophic lateral sclerosis—also known as ALS, or Lou Gehrig’s disease—and forced into early retirement. “Thirty-seven years at Cat, you know, two sick days and 12 months from potentially being the CEO of the company, when you get an ALS diagnosis, and you’ve got two to five years to live,” he recalled to Fierce Biotech Research in an interview. Rapp, 67, has clearly outlived that prognosis and has taken advantage of the extra time by channeling his ambition into the quest to find better therapies and diagnostic tools for ALS. Now, he’s co-chair of a working group in a new effort to change how the disease is diagnosed and treated: the Accelerating Medicines Partnership in Amyotrophic Lateral Sclerosis, or AMP ALS, a five-year, $60 million public-private partnership announced May 21 by Foundation for the National Institutes of Health (FNIH), an independent nonprofit that supports the work of the NIH. “This is the first time we’re going to have all the leading organizations working in ALS from the for-profit side and the non-profit side working together,” Alessio Travaglia, Ph.D. director of neuroscience at the FNIH, said. “That’s the main reason why this initiative is going to be so powerful.” Slow progress Despite advances in research, therapies and massive awareness campaigns, the prognosis for ALS patients hasn’t moved much in the last few decades, Dave Shulman, 46, a Wells Fargo executive who was diagnosed with ALS in 2023, told FBR. “[When I was first diagnosed,] I wondered, 'Why are we 10 years out from the Ice Bucket Challenge, over 80 years out from Lou Gehrig’s famous speech, and more than 150 years out from when ALS was first identified by a researcher, and we’re still not at a place where we can meaningfully slow, stop or reverse the disease?'” he said. “And what are the underlying reasons why so many ALS clinical trials fail?” Recent years have seen some big steps forward, like the 2023 FDA approval of Biogen and Ionis Pharmaceuticals’ Qalsody, or tofersen, which slows symptom progression in ALS patients with a mutation in the protein SOD-1. But that subgroup makes up just 2% of the disease population. The two drugs that are FDA-approved for all ALS patients, Covis Pharma’s Rilutek and Mitsubishi Tanabe’s Radicava, have only “modest” effects, according to James Berry, M.D., a neurologist and ALS researcher at Massachusetts General Hospital. “We are lucky to be in an era when we have seen the development of newer more effective therapies for ALS than ever before,” Berry said in an email. But the tempered efficacy of ALS drugs that work across subtypes suggests that they might be acting on mechanisms that occur after damage-causing cascades are already underway, he explained, which limits how much of an impact they can have, even if they do apply to all patients. Other major drawbacks, like the removal of Amylyx’s ALS drug Relyvrio from the market in April, underscore the challenge of developing ALS drugs. “So, while we do have more treatment options today than we have ever had in the past, we still have a long way to go,” Berry said. ALS is a complicated disease, to put it mildly. And while decades of research have lent insight into the basic mechanisms and the contribution of factors like SOD-1 mutations, there’s still a black box around its natural course and what kinds of biomarkers are associated with progression, Steph Fradette, vice president and head of neuromuscular development at Biogen and a steering committee member of AMP ALS, told FBR. “The foundational challenge is that we’re still coming to understand the underlying pathophysiology of ALS,” she said. “There are exceptions to that rule and we are making a lot of progress as a field, but we still have a lot of uncertainty about what is actually causing the disease, what are the downstream implications of that cause and then, of course, how to address it.” The win with Qalsody aside, Biogen like other companies has weathered its share of ALS drug failures, most recently with an Ionis-partnered candidate called BIIB105. That drug wasn’t as far along as the company’s first attempt at an ALS therapy—dexpramipexole—which failed a phase 3 trial in 2013, but it suffered from the same blind spots with regards to efficacy. “Over the past several years we’ve found ourselves, like with dexpramipexole, in a situation where we have false positive and false negative trial results,” Fradette said. That has led to conversations within the field about what endpoints are really indicative of progress as well as about the tools used to measure them, she added. That’s not to say there’s been no improvements, of course: Qalsody was approved on the basis of reductions in a marker called plasma neurofilament light chain (NfL), a protein that is increasingly being used as an indicator of neuronal damage in neurological drug trials. But it took longer to get NfL assays out of academic labs and into industry practice than if an initiative like AMP ALS had existed, Fradette said. And it’s hard to go further without knowing how the disease progresses naturally—which is impossible without biological samples from patients, both living and deceased. Although there are currently disparate efforts to collect these on the part of government and nonprofit organizations, there are still too few, Travaglia said. “We don’t have enough post-mortem samples or longitudinal samples. We have to rely on just one single data point, meaning we take patients today and analyze those samples, but we don’t know how those biomarkers are going to progress,” he explained. Beyond a shot in the dark The ALS AMP’s database will fill in the knowledge gaps by first compiling existing data from various entities then getting more from patients and those at risk of ALS based on what’s missing. Seven biotechs, seven nonprofits and two government agencies—the FDA and the NIH's National Institute of Neurological Disorders and Stroke—are involved in the creation of the database. Representatives from the entities will sit on a steering committee that decides what information is needed, then the FNIH and NIH will put out requests for proposals and issue grants to researchers to collect it. “More than anything, I think that bringing together these different datasets and knowledge across the different people at the table will help accelerate that understanding in a way that anyone or group of us can do on our own,” Fradette said. Besides identifying biomarkers and therapies that might be useful for ALS patients in general, the effort may also delineate groups of patients with certain genetic factors that cause them to develop ALS, like those with the SOD-1 mutation. This could eventually make it possible to treat ALS with personalized medicines like the ones used for cancer, Julie Gerberding, M.D., president and CEO of the FNIH, said in an email. “The program will focus on comprehensive data collection and analysis that can help identify subgroups within the ALS population,” Gerberding said. “These subgroups might have distinct underlying causes that will allow researchers to develop targeted therapies specific to the subgroups.” For Rapp, Shulman and many other patients who are involved in AMP ALS, progress can’t come soon enough. “There is pretty good acceptance that ALS is not a single disease—it’s more like cancer where you have different variations,” Rapp said. “But until you understand that, I think any drug trials are a bit of a shot in the dark because you’ll never know if you have the right subgroup of patients.” Editor's note: This article was updated May 29 to clarify that the FNIH is an independent nonprofit and to update the number of biotechs, partners and nonprofits participating in AMP ALS, as well as to adjust some details about how the program works. Travaglia's last name was also misspelled in an earlier version and was corrected.

临床3期高管变更

2024-02-25

·MedCity News

Lose Fat, Not Muscle: Next Test for Lilly’s Zepbound Pairs It With BioAge Drug

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

临床2期临床1期临床3期

2024-02-23

·药智网

仅凭1款药品，如何在A轮融到30亿？

4.25亿美元！还只是A轮！还只有一款在研产品！上周，国外一家名为Areteia Therapeutics（以下简称Areteia）的Biotech公司宣布完成完成7500万美元的额外A轮融资，使A轮融资总额达到4.25亿美元（约30.57亿元）。投资者中不乏GV、赛诺菲、ARCH Venture Partners等国外知名投资机构的身影。在如今的资本寒冬里，4.5亿美元的A轮融资可谓相当“炸裂”，梳理今年年初的主要融资事件，许多初创企业A轮都只能融到可怜的几千万元，能过亿，就很不容易了。“还是美国融资环境好啊。”不少行业人士发出这样的感叹。然而放下艳羡的情绪，会发觉Areteia有不少特殊之处，能在A轮融到4.5亿美金或许也不足为奇：产品虽仅有右旋普拉克索，但十多年前估值就达数亿美元，如今正进行临床III期试验。更进一步，如果要回顾Areteia的诞生历史，更是能理出一部寒冬中Biotech生存指南：孵化方Knopp Biosciences一边剥离Areteia独立融资，一边将团队+技术平台打包“卖身”，使得产品开发价值最大化的同时，又保证了自身生存，真是下了一盘好棋。或许这个案例告诉我们，天上从来不会掉馅饼，想成功，信心和坚持是基本的，但同时也要足够聪明、懂得变通。当灵活的商业模式架构和坚持不懈结合到一起，便造就了一段寒冬中的佳话。01仅凭一个产品如何在A轮融到30亿？如果要回答这个问题，必须要回到基本面。俗话说得好，台上一分钟，台下十年功。看背景，Areteia只不过是一家2022年才成立的公司，至今不到两年，由生物技术公司Knopp Biosciences联合私募股权机构Population Health Partners共同创立。成立当年，美国生物技术资本市场早已进入下行周期，Areteia却上演了一场逆风飞扬。凭借3.5亿美元A轮融资，Areteia便上榜行业媒体Fierce Biotech发布的“2022年全球融资最多Biotech榜单”，成为那一年获投资者最为青睐的公司TOP10之一。而今，再获7500万美元的额外A轮融资。一路走来，Areteia如此受资本青睐，背后实则离不来其产品和团队的强力加持。先看产品本身，Areteia仅一款产品——治疗嗜酸性哮喘的右旋普拉克索，正在进行临床III期试验。不过，右旋普拉克索实则“大有来头”。在交至Areteia手中时，该产品便已走到了后期临床试验阶段，开展较为顺利。故事还得从孵化方Knopp Biosciences说起，该公司成立于2005年，早期做了不少准备工作，一些弯路也大多趟平了，为Areteia顺利开展右旋普拉克索的临床试验积累了不少经验。早在2010年，Knopp Biosciences就和渤健合作一起推进右旋普拉克索在渐冻症领域的应用。当2013年渤健宣布III期临床试验失败后，开发者大失所望，认为渤健的试验设置流程有问题，要求对方给出详细的入组患者数据，双方还一度闹到了对簿公堂的地步。但不管怎么闹，怎么失败，渤健的青睐都给出了这款药的最初估值——2010年BD合作总额就高达3.45亿美元。当然，Knopp Biosciences没有放弃过对右旋普拉克索的信心，一直在想办法找钱，转变适应证，直到发现了其对嗜酸性粒细胞的抑制作用，一切才有了转机。在Knopp Biosciences手中，右旋普拉克索从立项走到了临床前研究再到2期临床试验。而为了在寒冬中将右旋普拉克索带入最费钱的3期临床，Knopp Biosciences在2022年做了一个思虑周全的决定，与资本联合创建了Areteia，希望能单独融资，并将右旋普拉克索带入后期临床试验。至此，一个含着金汤匙出生的富二代宣布诞生。更重要的是，右旋普拉克索所对应的重度嗜酸粒细胞性哮喘市场前景也构成了投资者对Areteia的巨大想象空间。一项统计数据显示，全球哮喘患者超过3亿，重度嗜酸粒细胞性哮喘占⽐高达83.8%。控制重度嗜酸粒细胞性哮喘成为了哮喘治疗的关键点，而对于这一病症，过去的常用疗法亟待改进。根据资料，该药作用原理类似于IL-5生物制剂，能抑制嗜酸性粒细胞的成熟和释放，降低嗜酸性粒细胞数量，进而改善肺功能。2021年9月，右旋普拉克索在中重度嗜酸性粒细胞性哮喘患者中开展的2期临床试验EXHALE结果表明，口服右旋普拉克索导致的患者嗜酸性粒细胞的计数减少与肺功能改善显著相关。试验达到其主要终点，显示出剂量依赖性的嗜酸性粒细胞减少，与患者支气管扩张剂前FEV1的改善显著相关。倘若右旋普拉克索能够顺利完成III期临床试验，获批治疗嗜酸性哮喘适应证，则有望成为成为该病的早期治疗手段，并成为嗜酸性粒细胞性哮喘首款获批的口服药物。Areteia的团队实力同样不容小觑。Areteia孵化后，虽然Knopp的身影早已消失在了行业内，但其Knopp的两位科学家创始人仍然是Areteia的董事，而他们也为Areteia找来了经验丰富的管理和研发人才进行“交接”。Areteia的首席执行官Jorge Bartolome对于Areteia的发展绝对“对口”。他曾是杨森加拿大公司总裁，还曾在GSK担任呼吸和神经科学业务的高级副总裁兼美国业务部负责人。而Areteia的首席科学官，来自右旋普拉克索最早的研发团队，在进入产业界前，他在监管界和学术界拥有丰富经验，曾在国家过敏和传染病研究所(NIAID)工作了二十多年，担任多项嗜酸性粒细胞相关疾病临床试验的首席研究员，还曾在FDA肺部过敏药物咨询委员会任职。此外，Areteia的首席医学官、首席商务官、供应主管等高管人才都来自GSK、BMS等MNC。值得一提的还有与Knopp合伙孵化Areteia的私募股权公司Population Health Partners，其投资脚步遍布全球，该机构专注于投资后期项目组建的公司，曾推动8项药物批准。也就是说，A轮4.5亿元的融资包含了一款市场潜力巨大的临床后期产品+拥有研发与管理能力双重加成的团队+业界知名机构背书。某种意义上，该决策很像当年雅培实验室将“药王”修美乐装进艾伯维，再挥一挥手让后者单飞上市。艾伯维吃到红利后，股价一飞冲天。如果分别计算雅培和艾伯维的股价上升幅度，甚至跑赢了同期追求“大”的强生，完全可以说是一次共赢。类似决策的背后，既体现了一个“老父亲”厚重的爱，其实也书写了Biotech在寒冬中的一部自救指南。02“裂解”式自救更进一步，会发现这个故事的第二层是美国生物科技公司生存战里积极自救的戏码，而且其手段对中国广大Biotech有着重要的借鉴意义。如果故事的主角变成孵化Areteia的Knopp，故事同样精彩绝伦。早在孵化前半年，2022年2月，Knopp Biosciences就将公司的主要研发负责人、研发团队以及Kv7钾离子通道靶向平台打包卖给了Biohaven，成为后者研发部门的一份子。如今从结果来看，Knopp这种平台资产“卖身”，分拆产品单独成立新公司的“裂解”式自救是当时该公司对行业环境的成功预判，也不失为生物技术公司在市场下行周期中自救的可行方式。几年以前，能够持续输出创新产品、构建产品组合优势的平台型公司所营造的创新泡沫环境一朝被打破，诸多Biotech创始人从Biotech向Biopharma的梦想也终成“天方夜谭”。伴随而来的是大批量生物技术公司裁员、砍管线，甚至最终因现金枯竭走向破产、倒闭。一位投资人对笔者表示，小型Biotech陷入困境中很重要的一个原因是，“他们过度关注平台技术，而不是最终可以赚钱的硬临床资产”。回到Knopp公司身上，作为一家未上市公司，它早早预见到了即将面临的困境：曾经与渤健合作的破裂，让核心产品右旋普拉克索即使找到新出路，手上的现金也难以为继；除了右旋普拉克索，公司开发十余年的潜在best-in-class产品Kv7钾离子通道激活剂KB-3061（BHV-7000）即将步入临床研发，又将是一大笔投入。同时，Knopp公司其实也已经嗅到了资本寒冬的气息，倘若继续靠自身造血，无论是手中FIC、BIC产品，还是历经十年打造的Kv7平台，或许都将因资源有限拖累进度，甚至极有可能让多年努力“付之东流”，而有了与渤健合作的“前车之鉴”，再通过合作换取现金流，不但受制于人，也恐难以实现在研产品的真正价值。是实现产品价值，还是实现创业价值？关于这个问题，Knopp选择了前者：团队和平台打包“卖身”并入Biohaven，后期产品右旋普拉克索单独成立新公司，聚焦单一产品。如今回顾这一决策，有运气成分，也有战略眼光，从结果来看，Knopp或许赢得了这场产品价值与市场环境的对赌。Biohaven成立于2013年，同样是含着科学的金汤匙诞生，由耶鲁大学的几位教授基于一项神经学新发现和专利联合打造而成，这也就使得Biohaven自诞生之日起，就一直聚焦于神经学新药的研发。同时在成立之后，经过多番BD与并购，Biohaven在短时间内实现了产品销售额收入，首个商业化产品获批2年就卖出了超5亿美元。值得注意的是，在2022年，Biohaven的CGRP相关资产已经被辉瑞以116亿美元收入麾下。这是笔双赢交易。背靠辉瑞的Biohaven也是Knopp的伯乐，时任Biohaven神经学副总裁的Irfan Qureshi认为Kv7平台与Biohaven现有的神经学产品线高度互补，所以保留了Knopp团队成员以及其开发计划。如今，Knopp已经成为Biohaven的离子通道研发部门，并依旧由原首席执行官David Pirman和首席科学官Steven Dworetzky担任部门负责人，BHV-7000也成为Biohaven五大核心产品之一，在2022年顺利进入临床试验，预计于2024年第一季度启动局灶性癫痫的2/3期研究。除了进行癫痫适应证的研究外，还开展了针对重度抑郁症、双相情感障碍和焦虑症等神经精神疾病的开发。总结来看，Knopp自救经历，其实可以写入一部Biotech寒冬生存指南的一个章节，它向行业证实了一个道理：生物技术公司创业平台不再是唯一追求，“卖身”大药企也不是唯一出路。只要真正心系产品，心系临床价值，“道”正了，合适的“术”自然呼之欲出。声明：本文2月22日首发于《E药经理人》（ID：eyjlr2013），经授权转载，如需二次转载请联系原作者。E药经理人媒体平台致力于成为医药行业意见领袖平台，记录和观察医药重大商业事件，展现行业的复杂与冲突，提供最前沿的思想洞见。阅读原文，是受欢迎的文章哦

临床3期临床成功

100 项与右旋普拉克索相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09887	-	-	DB15130

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
嗜酸性粒细胞性哮喘	临床3期	美国	Areteia Therapeutics, Inc.初创企业	2024-05-08
肌萎缩侧索硬化	临床3期	美国	Knopp Biosciences LLC	2011-03-01
肌萎缩侧索硬化	临床3期	澳大利亚	Knopp Biosciences LLC	2011-03-01
肌萎缩侧索硬化	临床3期	比利时	Knopp Biosciences LLC	2011-03-01
肌萎缩侧索硬化	临床3期	加拿大	Knopp Biosciences LLC	2011-03-01
肌萎缩侧索硬化	临床3期	法国	Knopp Biosciences LLC	2011-03-01
肌萎缩侧索硬化	临床3期	德国	Knopp Biosciences LLC	2011-03-01
肌萎缩侧索硬化	临床3期	爱尔兰	Knopp Biosciences LLC	2011-03-01
肌萎缩侧索硬化	临床3期	荷兰	Knopp Biosciences LLC	2011-03-01
肌萎缩侧索硬化	临床3期	西班牙	Knopp Biosciences LLC	2011-03-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04046939 (EXHALE-1, Biospace) 人工标引	临床2期	肺嗜酸性粒细胞增多	103	dexpramipexole 37.5 mg	-	积极	2023-08-03
NCT04046939 (EXHALE-1, Biospace) 人工标引	临床2期	肺嗜酸性粒细胞增多	103	dexpramipexole 75 mg	-	积极	2023-08-03
NCT01622088 (CTgov)	临床3期	肌萎缩侧索硬化	616	Dexpramipexole (Dexpramipexole 150 mg BID)	構鏇獵壓壓糧願遞壓鏇(鬱膚醖觸膚窪鬱蓋鬱夢) = 鏇膚獵壓構觸鑰願鹹獵繭壓繭選餘襯憲齋壓蓋 (選衊簾簾糧顧積衊鹹齋, 膚齋餘範繭齋遞簾襯淵 ~ 繭選遞廠膚簾鑰積膚膚) 更多	-	2022-04-07
NCT01622088 (CTgov)	临床3期	肌萎缩侧索硬化	616	Dexpramipexole (Dexpramipexole 300 mg/Day)	鏇顧願鬱鬱鹹觸獵餘鬱(獵淵艱蓋蓋繭夢獵廠網) = 餘鬱壓構餘選齋選積範範醖繭淵觸顧鑰繭襯襯 (顧顧糧製襯願選衊鏇獵, 製獵範憲獵衊範積鬱積 ~ 淵憲鹹獵範廠壓鑰範積) 更多	-	2022-04-07
NCT01388478 (CTgov)	临床2期	阿尔茨海默症 \| 认知功能障碍 \| 应激氧化	20	R-pramipexole	簾願獵膚選壓簾鬱鬱構(鹽獵膚蓋鏇鹽網觸選繭) = 衊鏇網繭淵夢蓋廠鏇齋蓋選醖襯選觸選繭醖膚 (鏇膚遞獵鏇夢選壓遞顧, 糧鹹淵獵選顧糧憲齋鬱 ~ 蓋顧選餘膚餘範夢簾蓋) 更多	-	2021-10-12
NCT00931944 (CL211, CTgov)	临床2期	肌萎缩侧索硬化	74	KNS-760704	鬱壓觸構齋衊鑰選糧窪(餘艱醖築鹽憲繭構鹹鹹) = 窪蓋齋鹽製窪網蓋膚糧鏇選鹹廠蓋簾憲構顧糧 (蓋製艱構鹽願夢顧鬱遞, 鏇鹽簾蓋糧繭膚觸膚鬱 ~ 窪鬱鏇鏇蓋齋醖網簾衊) 更多	-	2021-08-16
NCT01281189 (EMPOWER, CTgov)	临床3期	肌萎缩侧索硬化	942	Placebo (Placebo)	遞餘鬱鏇顧廠衊鹹繭觸(簾製築膚鏇糧蓋夢窪網) = 糧遞構糧醖膚憲齋積鏇鏇網範憲積製鏇艱簾憲 (齋衊觸衊積網糧蓋鹽簾, 膚蓋襯網鏇淵壓鹽築製 ~ 顧齋繭淵餘膚鹹廠鬱鬱) 更多	-	2021-06-07
NCT01281189 (EMPOWER, CTgov)	临床3期	肌萎缩侧索硬化	942	Dexpramipexole (Dexpramipexole)	遞餘鬱鏇顧廠衊鹹繭觸(簾製築膚鏇糧蓋夢窪網) = 鏇觸顧顧廠繭繭鹹範壓鏇網範憲積製鏇艱簾憲 (齋衊觸衊積網糧蓋鹽簾, 廠遞鏇膚窪簾鬱積艱獵 ~ 願淵鹹顧遞繭壓齋鏇蓋) 更多	-	2021-06-07
NCT02217332 (CTgov)	临床2期	高嗜酸性粒细胞综合征 \| 鼻息肉 \| 慢性鼻窦炎	20	dexpramipexole	壓壓繭簾糧鹽簾範鹽遞(繭鑰築廠壓網範淵淵鏇) = 廠餘選膚鹹築夢網憲鏇顧衊構齋製網構夢願鏇 (鏇蓋廠齋觸廠選齋選獵, 蓋醖鬱製鹹窪選醖築簾 ~ 醖製餘築構鹹鹹窪淵襯) 更多	-	2021-05-18
NCT02101138 (Pubmed \| Blood) 人工标引	临床2期	高嗜酸性粒细胞综合征	10	Dexpramipexole Dihydrochloride	壓糧選築憲顧艱壓鏇鏇(顧顧願觸糧壓築網願夢) = 願襯鑰遞鏇遞鏇簾夢繭壓衊鏇鹹醖鏇製醖鬱鬱 (鬱醖壓製醖壓餘鏇構醖, 6 ~ 98) 更多	-	2018-08-02
AAAAI2017	N/A	慢性鼻窦炎伴鼻息肉 blood absolute eosinophil count (AEC)	-	Dexpramipexole 300 mg/day	顧淵膚憲積壓網願齋鬱(齋衊糧鹽襯鹹積繭簾鹽) = 簾夢膚夢範製製廠鏇鑰繭願顧積襯顧糧蓋築願 (範憲築構積積簾鏇築築 )	积极	2017-02-01
NCT01281189 (EMPOWER, Pubmed \| Lancet Neurol)	临床3期	肌萎缩侧索硬化	943	Dexpramipexole 150 mg	糧廠鹹積憲淵衊糧鹹築(齋網艱夢網衊顧鏇積簾) = 憲繭獵鑰鏇網遞衊襯夢繭簾範蓋選顧蓋壓積積 (蓋願壓繭鬱鹽齋構網鬱 )	不佳	2013-11-01
NCT01281189 (EMPOWER, Pubmed \| Lancet Neurol)	临床3期	肌萎缩侧索硬化	943	Placebo	糧廠鹹積憲淵衊糧鹹築(齋網艱夢網衊顧鏇積簾) = 觸齋簾艱憲鹹鬱製遞網繭簾範蓋選顧蓋壓積積 (蓋願壓繭鬱鹽齋構網鬱 )	不佳	2013-11-01