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Deep Genomics' BigRNA was built out of 1 trillion genomic signals captured from thousands of datasets, and includes 1.8 billion tunable parameters. Deep Genomics is taking two emerging technologies—which in recent years have captured the public’s attention for different reasons—and is finding they can work great together. The company has put forward an artificial-intelligence-powered foundation model designed to explore RNA biology, and how the small pieces of genetic material can contribute to various diseases or provide avenues for new therapies.  AI foundation models, as a category, describe systems trained on massive amounts of information that can then be tailored to produce a variety of different outputs—this family includes the recently popular text and image generators such as ChatGPT and other programs. RNA research, meanwhile, famously demonstrated its potential in the COVID-19 vaccines developed by Pfizer, BioNTech and Moderna, and is currently being explored for a range of diseases. Deep Genomics’ AI, dubbed BigRNA, is a transformer neural network designed to predict the biological mechanisms that regulate RNA expression tissue-by-tissue, to help better understand how specific variants in genes ultimately give rise to different diseases. At the same time, the program can identify potential binding sites for proteins and microRNAs, which could possibly be exploited for the discovery and development of new drug compounds. “Building machine learning models that can predict gene expression from DNA sequence has been a long-standing research goal, and one that has seen significant strides owing to recent advancements in deep learning,” Brendan Frey, Deep Genomics’ founder and chief innovation officer, said in a statement. After being given a DNA or RNA sequence, the AI can examine the effects of non-coding genes, as well as mutations that may or may not alter the ultimate function of a particular protein, and then help design matching RNA-based therapeutics, Frey said. “In a comprehensive study of 14 genes, BigRNA consistently designed highly effective steric blocking oligonucleotides that act in a tissue-specific manner, including for genes involved in Wilson disease and spinal muscular atrophy,” Frey added.  By intervening in how cells process RNA, these oligonucleotides could potentially help reverse the effects of a disease-causing genetic variant, by blocking the overproduction of a troublesome protein or increasing the production of a deficient one. BigRNA was built out of 1 trillion genomic signals captured from thousands of datasets, and includes 1.8 billion tunable parameters, the company said. The details of the model were published on the journal preprint site BioRxiv. The company said it also plans to present its data at future scientific meetings.  The computer model looks to deliver on Deep Genomics’ long promise that AI can help deliver gene-based therapies that can be programmed for different objectives. The Toronto-based company raised $180 million in a 2021 series C venture capital round with a pitch to advance research on at least 10 computer-designed drugs.  Currently, its pipeline lists a handful of undefined preclinical programs in metabolic and central nervous system diseases, though it previously identified Wilson disease as a target—a rare genetic condition where excess copper is stored within the body’s tissues. Earlier this month the company made a change to its leadership. It appointed Brian O’Callaghan to serve as CEO, while Frey transitioned from the position to chief innovation officer. “I’m proud of the team, the progress we have made, and the molecules we are advancing through animal studies, and I look forward to sharing updates on recent achievements in the months ahead,” Frey said in a September 15 release. O’Callaghan most recently held the top spot at ObsEva, the women’s-health biotech that restructured its C-suite earlier this year in a bid to save cash, ahead of its delisting from the Nasdaq in March. He has also served as CEO of Petra Pharma, Acucela, Sangart and BioPartners.

Editors note: BioPharma Dive, as part of its newly launched Emerging Biotech Weekly, is taking a closer look at competitive areas of startup activity. We aim to give an overview of the companies developing a new technology and what their goals are. This, on TYK2 inhibitors, is our fifth.When one drugmaker succeeds, many others try to do better.Thats one reason why a protein called TYK2 has fast become one of the biotechnology industrys top targets. At least a half dozen startups have set out to develop drugs that block it to better treat autoimmune diseases.Conditions like psoriasis and arthritis affect millions of people. For years, they have been treated with injectable drugs like AbbVies Humira, which are among the sectors most lucrative products.Drugmakers have sought to replace them with more convenient oral medicines, but with mixed results. Pfizer, AbbVie and Eli Lilly, for example, each brought to market pills that target a family of proteins known as Janus kinases, or JAKs, which are involved in the bodys immune response. The drugs have proven effective at treating a wide range of inflammatory diseases, yet their use has been curtailed due to safety concerns.Enter the TYK2, or tyrosine kinase 2 protein. Though part of the broader JAK family, TYK2 is viewed as a potentially safer target by scientists and drugmakers. That thinking was reinforced in September, when the Food and Drug Administration approved Bristol Myers Squibbs Sotyktu for moderate-to-severe psoriasis without the safety warnings that have limited its JAK-blocking competitors.Now the race is on to surpass Sotyktu. At least one startup developing a TYK2 inhibitor has launched since Sotyktus approval, while two other companies raised fresh funding to push their drugs further along.Success could mean significant financial gain. Bristol Myers, which is also testing Sotyktu in psoriatic arthritis, lupus, and Crohns disease, forecasts yearly sales of Sotyktu could eventually reach as high as $4 billion.Heres where things stand.What are TYK2 inhibitors and how do they work?TYK2 inhibitors work by blocking the TYK2 protein and the cellular signals that run through it. Those signals can in turn activate other immune proteins and are associated with inflammation.Disrupting that signaling by targeting TYK2 is viewed as a promising way to tamp down excessive inflammation brought on by autoimmune diseases such as psoriasis, psoriatic arthritis, Crohns disease and lupus.Another part of the attraction of TYK2 inhibitors is they offer a way to target inflammation without also blocking related JAK proteins, the inhibition of which can cause serious side effects.The first approved JAK inhibitor, known as Jakafi, was discovered by biotech company Incyte and developed for myelofibrosis and graft-versus-host disease. Since then, drugmakers have poured hundreds of millions of dollars into development of JAK blockers for autoimmune conditions, leading to Pfizers Xeljanz, AbbVies Rinvoq and Eli Lillys Olumiant. All three are approved for rheumatoid arthritis, as well as conditions like psoriatic arthritis that are being targeted by TYK2 developers.But while JAK inhibitors intrigued researchers because of their ability to block multiple inflammatory cytokines, that kind of broad effect has also been their weakness.What advantages do TYK2 inhibitors have over other treatments?So far, TYK2 inhibitors havent been linked to the serious health problems that have been reported in testing of JAK inhibitors.In clinical studies, some patients taking the JAK inhibitors developed by Pfizer, AbbVie and Eli Lilly developed infections and blood clots, meriting an FDA warning on the drugs labeling. Additionally, a study comparing Pfizers Xeljanz to drugs like Humira showed a higher rate of cardiovascular complications and cancer. That finding led to the FDA to require JAK inhibitors be used only in patients who cannot take or dont respond to those drugs.While infections were observed in testing of Sotyktu, the majority werent serious and did not lead to patients discontinuing treatment. The FDA didnt include boxed warnings of the risk of clotting, cancer or heart complications on Sotyktus labeling, either, despite some concerns the agency might consider anti-TYK2 drugs as similar to JAK inhibitors.Doctors can also prescribe Sotyktu without requiring patients first try biologic drugs. In testing, Sotyktu bested Amgens Otezla, an oral treatment for psoriasis that works differently, indicating TYK2 blockers can be potent options for clearing skin, too.As pills, TYK2 blockers are also more convenient than injectable drugs, such as Humira or newer medicines like Novartis Cosentyx, which are widely prescribed.Which companies are developing TYK2 inhibitors?Aside from Bristol Myers and Galapagos, another large drugmaker working on a TYK2 inhibitor, a handful of startups have cropped up to break into the field.One of the splashiest is Priovant Therapeutics, a startup spun out of Pfizer and Roivant Sciences in June with two TYK2-targeting candidates. Pfizer holds a 25% stake in Priovant, which has not raised additional funding.The most well-funded, Nimbus Therapeutics, has raised at least $400 million in private financing for development of its TYK2 inhibitor and other drug candidates, according to the company. Adding in partnerships and other deals, the company has to date received more than $1 billion, Nimbus company CEO Jeb Keiper recently told BioPharma Dive.Select list of biotech startups developing TYK2 inhibitorsCompanyLead InvestorsAmount RaisedNimbus TherapeuticsRA Capital Management, BVF Partners and AtlasAt least $400 millionAlumis TherapeuticsForesite Capital, AyurMaya$270 millionNeuron23Westlake Village BioPartners, Kleiner Perkins, Redmile Group, SoftBank$213.5 millionSudo BiosciencesFrazier Life Sciences, Velosity Capital$37 millionSOURCE: CompaniesAnother company, Alumis, is working on a TYK2 inhibitor as well. Formerly known as Esker Therapeutics, the company raised a Series B round in January that brought its funding total to $270 million.Ventyx Biosciences went public in 2021 with a $152 million initial stock offering, and in September added another $177 million in financing.Sudo Biosciences is the latest company to launch, emerging from stealth two weeks after Sotyktu reached market.What is the status of their research?The clean label given to Sotyktu has brightened the prospects of would-be competitors.Furthest along in testing is Priovant, whose lead candidate, brepocitinib, blocks both TYK2 and JAK1. Unlike Bristol Myers and other startups, Priovant isnt focusing on psoriasis. The company started a Phase 3 study in the spring testing brepocitinib for a rare skin and muscle disorder called dermatomyositis, and is evaluating the drug in lupus as well.Alumis, meanwhile, began a Phase 2 trial of its drug in plaque psoriasis in late September and said it plans to start more mid-stage studies in the near future.Galapagos has reported results from a Phase 1 trial of its TYK2 inhibitor in psoriasis, and a Phase 2 trial in dermatomyositis is expected to start by the end of 2022. A rival psoriasis drug developed by Ventyx has also read out Phase 1 results.Other companies are nearing the clinic. Startup Neuron23 is working on a drug candidate that it expects to push into preclinical studies by early 2023, the company said.Ventyx, Sudo and Nimbus have each claimed their drugs could be more selective and potentially more effective than Sotyktu. They have a ways to go before they can prove that claim with clinical trial data, however. '

专注于内分泌领域未被满足的临床需求，并“做精、做深、做强”是维昇药业CEO卢安邦为公司规划的未来愿景。 进入2022年，维昇药业正加速实现这一愿景。 随着1月10日苏州本土化研发制造基地的奠基，标志着维昇药业正从从专注临床开发的初创公司走向拥有本土化生产制造与商业化能力的生物制药企业。 在公司核心产品研发与商业化团队日渐壮大、首个在研核心产品预计2022年年内递交上市申报的背景下，维昇药业从研发、生产到商业化的研产销一体化布局日趋完善，从Biotech转变为Biopharma的脚步不断加快。 在这个尚处于蓝海的赛道，成立至今仅三年多的维昇药业，正在向我们展现其致力于国内内分泌疾病治疗领域药物创新研发的决心以及打造内分泌创新药全链条的实力。 01、看到需求，改变现状 据悉，苏州研发制造基地一期完工后有望实现隆培促生长素的本地化生产。这一产品正是维昇药业有望在国内获批的首款产品。 去年8月，Ascendis公司的Skytrofa（隆培促生长素）在美国FDA获批上市，这是美国FDA 40年来首个批准上市的用于治疗儿童生长激素缺乏症的长效生长激素。 几十年来，儿童生长激素缺乏症的常规治疗是生长激素每日一次注射，以改善生长和代谢。但每天注射可能导致患者依从性差，容易漏针，进而降低整体治疗效果。与每日一次的短效生长激素相比，每周一次注射的长效生长激素可将注射频次大幅下降86%，能够极大程度地提高治疗依从性。 根据Frost&Sullivan发布的数据，预计到2030年全球儿童生长激素缺乏症的治疗的市场规模将达到60亿美元。目前全球已上市可用于儿童生长激素缺乏症的长效生长激素仅有在中国获批的金赛药业的金赛增以及韩国BioPartners与LG开发的另一款在韩国上市的药物。 为何用于儿童生长激素缺乏症的长效生长激素市场几乎是空白？包括基因泰克、诺和诺德、辉瑞等众多全球生物制药公司纷纷折戟，即使MNC们不断投入巨资开发疗效不劣于短效rhGH的长效制剂，但由于长效rhHG的研发难度极高，已有多款产品退市或停止研发。 数据显示，中国4-15岁的广义矮小症患者约为500万，治疗率不及5%，且平均治疗时间少于1.5年。对疾病认知的不足，加之目前治疗方式导致的患者依从性问题，使得很多患者或未接受治疗，或漏针导致疗效不佳。 作为Ascendis与维梧资本合资建立的维昇药业，在成立之初便拥有由Ascendis专利技术平台TransCon (Transient Conjugation，暂时连接)研发出的三个内分泌创新药（包括2021年在美国获批上市的隆培促生长素）在大中华区（包括中国内地、香港、澳门和台湾）独家开发、生产及商业化上市的权益。 2019年10月，维昇药业TransCon人生长激素的III期临床试验申请获得NMPA批准，在中国开展治疗儿童生长激素缺乏症的III期临床研究。2021年3月，中国III期临床试验已按期完成患者入组目标。提到III期临床试验，卢安邦自豪地说：“我们一天也没落下。”据悉，在2021年3月底完成入组原是2019年底疫情未发生时推定的日程。受疫情影响，临床试验一度中断4个月，但维昇团队依然抢回疫情耽搁时间，按时完成入组。随着后续临床顺利推进，维昇预估该款药将在今年年内向国家药监局提交上市申请，最快有望于2023年在中国上市。 隆培促生长素也有望成为中国首个未经修饰的长效人生长激素，每周一次使用，可持续释放与每日一次制剂同样的人生长激素。 隆培促生长素在美国FDA的获批，也意味着其采用的TransCon技术成功得到验证。 TransCon（Transient Conjugation, 暂时连接）技术是一个用于新药开发的创新技术平台，旨在创造优化治疗效果的新疗法，包括疗效、安全性和给药频率。TransCon技术可广泛应用于蛋白质、肽或小分子的多个治疗领域，并可系统性或局部使用。 除了隆培促生长素外，维昇药业还有2个产品运用了TransCon技术且正处于临床后期：包括一种用于治疗甲状旁腺功能减退症的甲状旁腺激素TransCon PTH；以及用于治疗软骨发育不全的长效C型利钠肽TransCon CNP。 维昇药业也同样获得了这两款产品的权益。目前，TransCon甲状旁腺素同样已进入国内III期临床试验阶段，TransCon C型利钠肽正在中国与全球同步开展II期临床试验。  不论是TransCon甲状旁腺素还是TransCon C型利钠肽，维昇都希望引进的新药产品能够改变当前的疾病治疗格局。以甲状旁腺功能减退症（HP）为例，全国目前约有40万患者。但是当前常规治疗手段为补充钙及维生素D，难以满足临床需求。内分泌治疗时常常是‘缺什么补什么’，而甲旁腺出问题却补不了PTH。维昇药业首席医学官杨军表示，“现在市场上有很多PTH相关产品，因半衰期短主要作用在成骨细胞，多适用于骨质疏松的治疗。而甲旁减需要持续平稳的血药浓度真正实现激素的替代治疗。当TransCon甲状旁腺素上市之后，现有治疗方式会得到大幅改善，并促进甲旁减治疗指南的调整。 Trans Con C-型利钠肽则针对治疗软骨发育不全。卢安邦介绍，软骨发育不全是造成短肢侏儒症最常见的原因，患者终身身高只有1.2-1.3m，全球预计约25万名软骨发育不全患者。但遗憾的是，目前国内尚未出现有效的治疗药物。如果Trans Con C-型利钠肽能够顺利获批上市，将有很大可能成为改变诊疗指南的药物。 “在新药引进过程当中，我们看到内分泌创新药领域的治疗方案和国外相比还是有提升空间。”卢安邦表示，维昇的每一款产品，都旨在改善目前内分泌治疗领域未被满足的临床需求。 02、打造研、产、销全链条布局 自2015年开始的药审改革以及一系列配套文件的出台，不断激发国内创新的浪潮，“大量地方、民间乃至国际资本的投入，掀起了药物创新的浪潮。政、产、学、研、用、金各部门的密切融合，加速了创新生态环境的改变。”医药政策专家这样认为。 正是在这一契机之下，2018年11月，由全球知名的医疗健康投资机构Vivo资本出资、拥有长效技术平台的生物制药公司Ascendis Pharma提供技术授权，卢安邦担任CEO并负责组建团队的维昇药业应运而生。“强力的政策导向以及巨大未满足的市场需求让维昇诞生在一个最好的时代。”卢安邦这样说。 随着此次苏州本地化研发制造基地奠基，意味着除了研发能力，生产与商业化能力也将成为维昇未来竞争的重要指标。研发、生产、商业化的综合实力也普遍被看作是从biotech成长为biopharma的必要条件。“在中国建设自主生产能力，能够灵活有效地加速实现管线产品的商业化，这是维昇进行创新药全链条布局的重大举措。”对于实现本地化生产这件事，维昇药业很坚定。卢安邦表示，本地化生产，首先可以保障药品供应的可持续性。同时，将优秀、先进的技术带到国内，助力整个产业的发展。另外不能忽视的是，中国拥有巨大的患者市场与临床需求，当我们掌握了所有生产流程与生产元素后，便可以进一步优化成本，从而提升患者的用药可及性。让更多中国内分泌患者受惠，也是维昇药业的承诺。 从在研管线来看，目前维昇的三款在研产品均处于临床后期，“随着未来在国内获批，我们将根据不同产品的特点与市场竞争环境，搭建与产品相适应的商业化平台。”维昇药业首席营销官陈军介绍到。 虽然不同产品将要覆盖的市场大小、现有市场规模、竞争环境各有不同，但商业化布局仍有相似之处。“维昇在做的都是同类最佳（Best in Class）产品，如何让医生了解我们的优势与特点，学术沟通是必不可少的。” 与此同时，针对患者端的疾病教育同样重要。“不论是内分泌疾病还是罕见病，很多患者对疾病本身的认知不足进而导致延误或错过最佳治疗时间，产生终生不可逆的后果，如何通过与学协会合作的疾病教育，改变认知，同样是我们在做的工作。”陈军博士这样说道。 除此之外，维昇也在加强与政府机构、专家以及其他疾病相关方的合作，完善患者教育与疾病科普工作。 在卢安邦的规划里，他希望将维昇打造成全世界内分泌创新药进入中国的门户，“未来苏州基地或可成为维昇药业的全球生产供应中心之一，让中国的生物制药产业更具全球竞争力，将更多的新药、好药带到中国来。” 作为公司的“1号员工”，卢安邦希望通过组建优秀的人才队伍，让产品能够更快地在中国落地，惠及更多中国患者。“目前维昇的员工拥有在跨国药企平均15年以上的工作经验，丰富的产品开发与上市销售经验能更好地帮助维昇实现产品研发、上市与销售。”卢安邦这样介绍。 在这之中，首席医学官杨军博士与首席营销官陈军博士便是典型代表。 据维昇药业介绍，公司首席医学官杨军博士于2020年4月1日加入，过去曾在礼来等MNC进行临床开发等工作。“她的加入让维昇的医学职能包括临床开发及医学事务团队越来越完整。” 在杨军博士加入的一年后，去年4月，曾在诺和诺德、礼来等公司从事商业化与营销工作的陈军博士加入并担任首席商务官。这一动作业界也普遍认为是“维昇建设核心商业化团队的重要举措”。 如今，在研产品进入上市申报在即、研发制造基地奠基、人才团队不断丰盈，维昇药业打造的研、产、销一体化的内分泌创新药领域全链条布局正在日趋完善。 在Biotech转变为Biopharma的道路上，维昇也将持续加速。 内容来源于网络，如有侵权，请联系删除，谢谢。