Yumanity, Inc.

Yumanity Therapeutics has struck two agreements to erase itself from existence. Johnson & Johnson has stepped in to take on Yumanity’s lead program and unpartnered discovery-stage candidates, while Kineta has laid claim to its Nasdaq listing and Merck collaboration through a reverse merger. Boston-based Yumanity sounded the alarm earlier this year, outlining plans to lay off 60% of its staff and seek a buyer for its assets. The actions followed the imposition of a partial hold on multi-dose trials of the biotech’s lead drug, stearoyl-CoA desaturase (SCD) inhibitor YTX-7739, that exacerbated its mounting cash crisis. Yumanity’s search for an exit has led to two deals, including J&J's Janssen Pharmaceutical unit picking up the biotech’s unpartnered pipeline. In return for $26 million in cash, the Big Pharma will secure the rights to YTX-7739 and unpartnered discovery-stage neuroscience product candidates and targets. YTX-7739 spearheaded Yumanity’s advance in its early years, helping it raise more than $100 million and then join Nasdaq through a reverse merger with Proteostasis in 2020. The interest in the molecule reflects evidence of the effects of SCD inhibition, which include the reversal of the toxicity of misfolded alpha-synuclein in mice. Yumanity moved YTX-7739 into a clinical trial in Parkinson's disease patients on the strength of the mice data, but its data drop received a frosty reception late last year. Investors drove down the share price of the biotech after seeing top-line data from a phase 1b clinical trial of 20 patients. The FDA compounded the situation by slapping a partial hold on YTX-7739 in January. With J&J picking off Yumanity’s in-house R&D programs, private immuno-oncology biotech Kineta has swept up the rest of the business. Shareholders in Kineta will own 85% of the combined biotech, which will retain the Kineta name and focus on immuno-oncology while continuing to support Yumanity’s research collaboration with Merck & Co. Merck formed the collaboration in 2020 to work with Yumanity on treatments for amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Late last year, Merck accepted the first data package from the collaboration, triggering a $5 million payment to Yumanity in a deal that could ultimately earn it $530 million.

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。2月29日，一家免疫疗法公司Kineta 宣布公司架构重组，裁员64%，解雇CEO辞职。此举旨在简化运营并专注于未来发展战略。受此影响，当日Kineta 股价下跌63%，市值降为852万美元。早在2022年6月，生物制药公司Yumanity Therapeutics宣布就两项战略交易达成最终协议。其中之一就是Kineta公司将在全股票交易中成为Yumanity公司全资子公司，合并后的上市公司将重新命名为Kineta, Inc.，该公司重点关注用于实体瘤的VISTA阻断免疫疗法，包括非小细胞肺癌、结直肠癌、肾细胞癌、头颈癌和卵巢癌。由于Kineta 的介入，将Yumanity免疫疗法拯救出来。然而现在，Kineta 需要自救。经过战略审查后，Kineta正在进行公司重组，并将员工人数减少 64%（即7 名员工，遣散费预计 241,000 美元），其中包括首席执行官 Shawn Iadonato 博士。Kineta新药KVA12123 的 1/2 期临床试验也将停止招募新患者，现有患者允许继续接受治疗。Kineta研发管线KVA12123是一种新型疗法——VISTA阻断免疫疗法（VISTA阻断免疫疗法通过阻断或抑制患者体内的VISTA分子，激活患者的免疫系统，使其更有效地识别和攻击癌细胞），给药频率每周两次，KVA12123单药在临床前模型中显示出强大的肿瘤生长抑制作用。提到KVA12123，不得不提免疫疗法之王K药（Keytruda），K药是FDA批准的第一款PD-1单抗。2022年10月，Kineta与默沙东达成合作，将KVA12123与K药联合用于晚期实体瘤患者。2024年1月，Kineta公布KVA12123的1/2期临床试验进展：KVA12123与K药联合治疗，在晚期实体瘤患者中显示出良好的临床活性和耐受性。截至2023年第三季度，Kineta手头有760万美元；而2022年底，它还有1310万美元。如今，现有资金只能维持公司到2025年初。同时，部分投资者表示，他们将不会履行预计今年4月份进行的第二轮融资义务。为了公司的发展，不得不进行战略重组、裁员、出售资产、清算等行动，以大幅减少开支并保留现金。参考资料：https://kinetabio.com/2024/02/29/kineta-announces-restructuring-and-exploration-of-strategic-alternatives/

Like many large pharmaceutical companies, Bristol Myers Squibb hasnt made brain drugs a top priority over the last decade.As a field, neuroscience represents a major opportunity for drugmakers. Alzheimers disease affects millions of people in the U.S. alone, and puts an enormous strain on the healthcare system. Patients with ALS, Huntingtons and other disorders hallmarked by the breakdown or nerve cells are in desperate need of new treatments.Yet, the complicated biology of the brain and central nervous system has led once-promising medicines to fail time and again, leading developers to pursue other areas of research like cancer, the immune system and rare diseases.The past couple years, though, have seen scientific and technological breakthroughs that have encouraged some of the most powerful and deep-pocketed pharmas to return to neuroscience. Bristol Myers is among them, having licensed experimental medicines from the biotechnology companies Prothena and Evotec. Last month, during a research and development event, Bristol Myers said it will be “re-establishing“ neuroscience as a therapeutic area of focus.BioPharma Dive sat down with Ken Rhodes, the companys vice president of neuroscience research, to discuss this re-entry and where brain drug development is headed. The interview, which aired during an Oct. 26 event hosted by BioPharma Dive and PharmaVoice, has been lightly edited and condensed.BIOPHARMA DIVE: Bristol Myers is reestablishing a therapeutic area of focus in neuroscience. What does that mean and why is the company making a statement of intent like that now?KEN RHODES: We can all agree that disorders of the central nervous system are increasing in prevalence. They're very serious diseases. There's clear medical need. And they represent some of the greatest challenges of our time, both in terms of their impact on patients, on caregivers, on families and on the healthcare system.So the desire to address devastating diseases like many of the neurodegenerative diseases is embedded within the DNA of the BMS organization.BMS has been investing in neuroscience for several years now. Obviously, we have [multiple sclerosis medicine] Zeposia but we actually have four programs that are about to enter Phase 2 development, all in the neuroscience disease area one in Alzheimers disease, another in ALS and then two others. And so with Zeposia and with this emerging portfolio, we have the underpinnings of a robust neuroscience pipeline, which we're looking to expand.We have a dedicated discovery team within the organization. We have some outstanding neuroscientists focusing on our internal portfolio, as well as the work we do with our collaborators at Evotec and Insitro, with several of our academic collaborations and with our broader interactions with the biotech ecosystem. Those folks partner with our clinical development organization and our commercial colleagues to think about how we're going to establish and ultimately deliver a robust portfolio of therapies to patients.Richard Hargreaves, who is the senior vice president for the neuroscience thematic research center, set out on a mission several years ago to put the CNS back in BMS. And I think if you look at the portfolio that Richard [and] the broader BMS organization put together, I think you quickly appreciate that that mission has been very successful.You mentioned Alzheimers and ALS. Whats driving Bristol Myers investment in those areas?RHODES: The themes are focusing around a well articulated construct that actually [Bristol Myers head of research] Robert Plenge articulated during the research and analyst day. And that is a strategy that focuses on causal human biology, matching therapeutic modality to the mechanism thats driving disease, and having a path to evaluate mechanisms and get to relatively early decisions on clinical activity.And that theme drives much of our decision making and how we make choices about what targets to pursue within the neuroscience area within BMS. If you look at the broader industry trends, some of the challenges that were faced in neuroscience drug discovery and development are when we drifted away from that central construct.What steps can you take to improve the odds of success? Are the tools available different than what you had five or 10 years ago?RHODES: The situation in drug discovery in neurodegenerative disease has changed dramatically even in the last five years, but certainly over the last 10 years. We have a much better and much deeper understanding of genetic drivers of neurodegenerative disease.Causal genes for Alzheimer's disease, for inherited forms of ALS, for multiple sclerosis to some extent, Huntington's disease have been fairly well elucidated and present some clear opportunities for therapeutic intervention.One of the things that has changed is our focus on those clearly defined mechanisms that are contributing to the initiation and progression of disease. This week in Boston is the Clinical Trials in Alzheimer's Disease, or CTAD, conference. One of the things that clearly comes out of the sessions at that conference is the integration of biomarkers into how we select patients for trials, how we monitor the impact of our therapeutic intervention on the disease process.Now with plasma biomarkers, with CSF biomarkers, with neuroimaging [and] PET imaging in particular, we can monitor the progression of disease longitudinally in living patients. And we can look at the impact of our drug candidates on the disease process using those markers as a way to be sure that our drug is in the target tissue and it's modulating the biology in a direction we believe will have therapeutic benefit. Then we can tie that ultimately to clinical outcome.Certainly the recent successes in Alzheimer's disease have benefited from the tremendous investment that has been made in the industry and in academia ... to enable a more biomarker-driven development strategy in neurodegenerative disease.Looking back on it, that is really what changed drug development in multiple sclerosis: the appreciation MRI imaging could be used to monitor disease and used to assess the impact of drugs on inflammatory mechanisms in multiple sclerosis. That has now catalyzed much of the investment in Alzheimer's disease and other neurodegenerative diseases, where we can use imaging and biomarker strategies to enable drug development in a way that just wasn't possible until very recently.One of the programs you mentioned is in Alzheimers. What biomarkers are you looking at?RHODES: The program you're referring to that's about to enter Phase 2 is a program with a monoclonal antibody targeting the microtubule binding domain of the protein tau.Its well established now in the field largely, again, as a result of imaging technology that actually it's the progression of tau pathology in Alzheimer's disease that is most closely correlated with clinical progression. So the dementia, memory deficits and other deficits in patients with Alzheimer's disease are tightly associated with progression of tau pathology and less tightly associated with the accumulation of amyloid.We have now a tremendous suite of biomarkers related to tau biology and amyloid biology that we will integrate into our clinical development program along, obviously, with clinical outcome measures. But I think the imaging component of that will give us a lot of information about whether our antibody is interacting with the tau protein and leading to tau removal from the CNS in Alzheimer's patients.Should we expect more business development activity in neuroscience?Rhodes: Most certainly you could expect to continue to see that.As long as the program targets a mechanism and that causal biology that we think is important, for the initiation and progression of disease, we would be interested in hearing about it and having a conversation about it.Together with our existing series of partnerships, we're certainly interested in evaluating other high quality opportunities that are consistent with our strategy. And that strategy really focuses on disease-modifying therapies in neurodegenerative diseases like Alzheimer's disease and ALS, in neuromuscular diseases and then neuroinflammatory diseases.Tell me about Bristol Myers program in ALS. Are any of lessons learned in Alzheimers relevant to drug development in ALS?Rhodes: Absolutely they are. Its another area where biomarkers have proven to be extremely valuable. And central to the approval of some of the more recent medicines for ALS is a reliance on a biomarker called neurofilament light chain, which is a marker of axonal degeneration in the central nervous system.Certainly an evaluation of neurofilament light chain would be part of any clinical development program we did in ALS, and likely a component of any clinical development program we did in any neurodegenerative disease. But it's another case where focusing on causal human biology is central to the strategy.This a program that targets integrated stress response. Protein misfolding is central to many neurodegenerative diseases, and as proteins misfold and accumulate they trigger a response called the unfolded protein response, which essentially shuts off protein synthesis within cells. [Thats] fine if it occurs transiently, but if it occurs chronically it can lead to profound stress on the cell, and cells will ultimately die and degenerate.This mechanism allows you to turn back on components of the integrated stress response and allow the cells to continue to function normally and, ideally, clear misfolded proteins. There's some really elegant pharmacology that was developed preclinically that set the stage for this program.You were previously at Yumanity, a neuroscience-focused biotech. What can pharma companies like Bristol Myers learn from biotech?RHODES: One of the things that small companies do very well is remain focused on their core mission. You commit to a platform, you commit to a target and you do everything possible to succeed and discharge risk and advance that program into the clinic. It's essential for the life of the company in a way, but it's really why everyone is there, working on these very difficult challenges.I had the tremendous pleasure of working with the late Susan Lindquist, who is a pioneer in many aspects of biology, but particularly around protein misfolding and its role in neurogenerative disease. At Yumanity, we had a very vibrant discovery platform and a very focused effort that ultimately led to entry into clinical development of a potential disease-modifying therapy for Parkinson's disease, which is now in the Johnson & Johnson portfolio.One of the things Id like to think we did well there was to remain focused and not chase too many shiny objects.I'm confident in saying that David Altshuler at Vertex likely said [during an Oct. 25 panel discussion hosted by BioPharma Dive] that this idea of multiple shots on goal is a bit of an illusion. And, I think in some cases, a bit of a distraction from really focusing on targets and mechanisms that are grounded in causal biology and should bear the bulk of the focus of our drug discovery efforts across the industry.I think that focus in a small company and everyone living or dying by the quality of the science is unique to a small company environment, and maybe something that could be learned from in large pharma. '