Many in the life sciences research community were spooked when PubMed went down temporarily in March after the Trump administration cut $4 billion in “indirect costs” that supported medical research. More recently, an ominous message appeared on PubMed: “Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed…” Many who use PubMed but not other government websites were probably panicked by this, but a quick look at clinicaltrials.gov, NIH Reporter and even NIH’s main site reveals the same message, while different versions of this message appear on the websites of HHS, CMS, etc.
Still, various EU governments have been quietly preparing for a PubMed shutdown by ensuring they will have a PubMed-alternative just in case. Of course, let’s be real: while they may be able to serve the existing content in PubMed, they will not be able to suddenly support the thousands of additional abstracts and articles added each day, along with MeSH tagging, journal selection, XML/JSON feeds, and other critical functions PubMed provides.
While PubMed is critical to nearly every life science researcher, even those with access to Web of Science, Embase, etc., it is especially critical to early-stage life science companies and investors. For basic research, competitive intelligence, due diligence and more, PubMed is indispensable for those without access to paid literature databases. PubMed is also an important source for pipeline database providers that investors and pharma use to find assets and perform CI.
The US government, for decades, has supplied a critical and reliable literature resource for worldwide audiences, both professional and non-professional alike. With the addition of the first and best clinical trial registry in 2000, continued funding for this resource is paramount for global biomedical research.
By Matt Stanton, VP Sales US West, Central and South America, LSN
JPM is creeping up on you once again, and you still don’t have an event planned. All the good venues are gone and all you’re left with are subprime ones or those with sky-high prices. Why not work with us to plan your best event or partnering table rental at the centrally located Marriott Marquis? RESI JPMwill be a two-day event this year: Monday and Tuesday. Life Science Nation has rental space available on Sunday, that will allow you to put your event during what is already a lively ecosystem of early-stage companies and investors. If you already have an event planned, why not do more? If there were ever a time to do more, it’s during JPM.
If you’re a membership organization, you owe it to your members to provide them partnering space at JPM. But getting a partnering table at one of the San Fran hotels will costs at least $1500 per day per table! Contact us to find out how you can get conveniently located partner tables for your members at affordable prices.
Finally, if you’re a product or service provider, sponsoring, exhibiting or attending RESI is, by far, the best opportunity to bang out 50+ meetings with early-stage innovators. RESI is the only partnering conference where companies are more than happy to accept partnering meetings with vendors, as can be seen in our partnering stats. In the RESI partnering system, you won’t find any profiles with the dreaded “no service provider requests”. Additionally, sponsoring or exhibiting at RESI is less than doing so at any of the other main JPM conferences.
Bilix, recognized as a top Innovator’s Pitch Challenge winner at RESI Boston this past September, is making waves in the biotech space with its innovative multi-modality approach to inflammatory and autoimmune diseases. In this interview, Myung Kim, Founder and CEO, shares how participating in RESI Boston helped the company connect with key investors, refine its strategy, and advance its clinical milestones.
Hear firsthand how Bilix is driving progress in complex disease treatment and discover how your company can join the next generation of innovators pitching at RESI London and RESI JPM. Applications are now open.
By Tony Jones, CEO, One Nucleus (Special Guest Contributor)
ELRIG, Life Science Integrates, Life Science Nation, One Nucleus and SLAS will provide delegates with the opportunity for cross-event partnering during London Bio-Innovation week, which runs 1-5 December, 2025
One Nucleus’ Genesis conference partnering app open to delegates attending any of Bio-Innovation Week events
Initiative to provide extended opportunities for networking, to support the life science ecosystem
London Bio-Innovation week, which runs 1-5 December, 2025, will see each of the five organisations delivering events in the UK’s capital city. While each event is being run independently, collectively their co-location in one city provides a unique opportunity to meet with in excess of 1000 of the brightest science and business minds in London that week.
To further support those seeking new collaborations, insights and opportunities, the event organisers will provide the opportunity for cross-event partnering. Delegates attending any one of the Bio-Innovation Week events will be able to access the One Nucleus Genesis app, to connect with delegates attending different conferences.
Tony Jones, CEO, One Nucleus, said: “Collaboration sits at the core of translating world leading bioscience research into new ventures developing innovative products and technologies to improve patient outcomes. With so much activity in London for Bio-Innovation Week, we identified a unique opportunity to support the life science sector, by opening the Genesis conference partnering app to both attendees and non-attendees, providing a platform for partnering across the multiple events.”
ELRIG are proud to be a leading European not-for-profit organisation dedicated to uplifting the life science and drug discovery community. Our mission is to foster open access to modern research and innovation. Bringing together our vibrant community of over 12,000 life science professionals from academia and biopharma to connect, collaborate and encourage curiosity.
Formed in 2011 by Christopher Watt and Samuel Thangiah, Life Science Integrates (LSI) brings together Senior Leaders from across the Life Sciences, including industry, academia, government and regulators; providing them with unique opportunities to be part of the conversations that set out the industry’s challenges and identify effective strategies and solutions.
The Redefining Every Stage of Investment (RESI) conference series, provided by Life Science Nation, connects start-ups and investors and strategic licensing partners. RESI maximizes fundraising companies’ efforts to find partners who are a fit for their technology and stage of development. RESI is uniquely cross-border and cross-domain, connecting start-ups with 10 categories of global investors across the silos of drugs, devices, diagnostics and digital health. RESI caters to both the earliest stage start-ups, those seeking grants, seed and angel capital, and the early-stage firms who seek series A and B funding. RESI is a unique and powerful tool for sourcing assets and advancing innovation across early-stage life science and healthcare.
One Nucleus is a not-for-profit Life Sciences & Healthcare membership organisation headquartered in Cambridge. We support institutions, companies and individuals in the Life Sciences sector providing local, UK-wide and international connectivity.
The Society for Laboratory Automation and Screening is the global leader in bringing life sciences researchers and laboratory technology providers together under one roof for knowledge sharing and collaboration aimed at transforming research. Annually, SLAS holds its must-attend International Conference & Exhibition in the U.S. and its Europe Conference and Exhibition, with opportunities for start-ups to gain exposure to thousands of potential customers, as well as award opportunities for scientific content by way of poster presentations and the annual Innovation Award. Regular networking events around the world enable regional communities to come together to strengthen research collaboration.
Commercial interest in targeted epigenetic therapies — agents that target specific genes without altering bases in their sequence or causing double-strand breaks or even single nicks in the DNA — continues to grow, as underscored by the latest financing announced by Epigenic Therapies. The unique selectivity and specificity of targeted epigenetic therapeutics offers compelling advantages over small-molecule epigenetic drugs, which target a specific epigenetic reader, writer or eraser, but affect genes across the genome and affect many diverse tissues, leading to narrow therapeutic windows that make them difficult to develop for conditions outside of cancer.
All of these therapies are designed around an alluring set of simple principles: take a gene-specific DNA-binding domain — zinc-finger proteins (ZFPs), ‘dead’ Cas9 (dCas9) with mutations in its RuvC and HNH endonuclease domains, or transcription activator-like effectors (TALEs) — and tether it via an amino acid linker to an enzymatic effector module. This effector is either an enzyme that directly places or removes a specific epigenetic modification (e.g., TET, histone demethylases or the histone acetyltransferase p300) or a transcriptional activator (e.g., VP16) or repressor (e.g., KRAB).
Epigenetic editing approaches have recently focused on dead CRISPR (dCRISPR) domains fused to various epigenetic effectors, but transcription activator-like effectors (TALEs) and zinc finger proteins (ZFPs) also continue to be explored. Source: TINS
A particularly compelling application for such treatments is genetic disorders of haploinsufficiency (like Dravet’s) or imprinting disorders (like Angelman’s or Prader Willi). There are also many of these diseases where the therapeutic genes would be too large (>4.0 kb) for a traditional AAV gene-therapy approach; in contrast, epigenetic editing machinery can be packaged into an AAV vector.
In a first paper published in Nature, the groups of Kevin Bender and Nadav Ahituv at UCSF (scientific co-founders of Regel Therapeutics) sought to test a targeted epigenetic therapy in patients with SCN2A mutations that exhibit decreased NaV1.2 function. These individuals have impaired action potentials, synaptic transmission and manifest diverse neurological symptoms and seizures, with few therapeutic options, beyond symptomatic anti-seizure medications that have a dizzying range of debilitating side effects.
The UCSF teams leveraged conditional genetic knock-in technolgoy or CRISPRa technology — an AAV-delivered SCN2A-promoter-targeting dCas9 fused to a VP16 activator domain — to upregulate transcription of the SCN2A gene. Using either approach, they were able to boost transcript levels from the healthy SCN2A allele, ameliorating electrophsiological deficits and chemical-induced seizure activity in Scn2a+/− mouse models. Importantly, these effects were seen in adolescent mice, which conventionally have been thought to be too old to respond to treatment. This suggests that rescue of normal dendritic excitability with epigenetic agents at later stages of life might be capable of restoring neuronal function, with implications for patients.
In a separate set of experiments, the authors showed that their epigenetic approach was able to rescue neurophysiological activity in haploinsufficient neuron-like cells from SCN2A-knockout human embryonic stem cells. This cross-species reproducibility provides further confidence that CRISPRa-mediated upregulation could be translated into human treatments.
In a second paper in Nature Biotechnology, a team from Epigenic Therapeutics (Shanghai, China) describes the design and validation of optimized epigenetic regulators (EpiRegs) to silence genes in a precise, durable way without altering genomic DNA. Epigen’s Shaoshai Mao and his collaborators at the Chinese Academy of Sciences and the First Affiliated Hospital of Anhui Medical University tested combinations of TALE- and dCas9-based systems, systematically optimizing effector domains and fusion architectures, looking for effective regulators of gene expression. The best-performing variant, EpiReg-T (a TALE-based system, which eliminates the need for a guide RNA), achieved 98% silencing of target genes in mice, substantially outperforming dCas9-based versions.
Using lipid nanoparticles (LNPs) for delivery, a single administration of EpiReg-T in macaques induced long-term repression of the PCSK9 gene, which encodes a validated target for the treatment of hypercholesterolemia. EpiReg-T reduced PCSK9 expression by >90% and LDL-cholesterol by about 60%, with effects persisting for nearly a year (343 days).
Mechanistically, the team used whole-genome bisulfite sequencing and cleavage under targets and tagmentation (CUT&Tag) to show that EpiReg-T induced stable DNA methylation and repressive histone marks at the PCSK9 promoter. The silencing persisted even after liver regeneration and could be reversed by targeted epigenetic activation. Multiomic analysis in mice, macaques and human hepatocytes confirmed high specificity of the manipulation and minimal off-target effects. Overall, these finding, as well as similar results reported in April by Chroma Medicine, establish epigenetic editing as a promising therapeutic platform for durable and reversible gene silencing.
Overall, targeted epigenetic therapies offer clear safety advantages over small molecules that indiscriminately target all genes under the control of an epigenetic eraser or writer enzymes. They avoid the potential risks associated with creating single- or double-strand DNA breaks associated with CRISPR/Cas9 gene, base or prime editing therapies. And they avoid the insertional mutagenesis risks associated with traditional viral gene therapies. What’s more, in applications requiring gene upregulation in haploinsufficient disease, these approaches maintain the endogenous regulatory context of the functional allele. This is in stark contrast to traditional gene-therapy replacement approaches, where overexpression of an introduced therapeutic gene can often lead to toxicities and immunogenecity.
Of course, questions still linger around the persistence of the changes elicited by these epigenetic agents. Will they persist in patients for long periods — for years or even decades? If they can, then epigenetic therapy may offer compliance advantages over small molecules, antibodies, ASOs or even siRNAs, which have treatment durations of six months or less.
Like all genetic medicines, though, delivery remains the key headache. Thus far, AAV vectors, lipid nanoparticles or ribonucleoproteins (RNP) have all been explored to deliver epigenetic therapies (with some evidence that RNPs might have advantages because they can result in higher dCas9 dosages within target cells). For AAV vectors, the fact that targeted epigenetic therapy might only need to be given once might be an advantage in terms of immunogenicity/neutralization concerns against the vector.
A broader point is that the safety profile of targeted epigenetic editors may offer advantages if AAV vectors are used as delivery vehicles: if the epigenetic agents themselves can be delivered at high dosage (given their intrinsic favorable safety profile and presumed maximal tolerated dose), perhaps AAV vector dosages could be lower than current practice. With many current gene therapies requiring dosages of 1013 or more viral particles/kg in patients, it is increasingly becoming clear that unacceptable liver toxicities arise from the virus at these levels in clinical studies. It will be interesting to follow this space as more agents enter human testing.
In this interview, Caitlin Dolegowski speaks with Cuong Do, Founder and Chairman of M6P Therapeutics, about the company’s groundbreaking lysosomal targeting platform, its applications in rare disease and oncology, and the experience of pitching at RESI Boston.
Caitlin Dolegowski (CD): M6P Therapeutics has achieved what was long thought impossible, delivering proteins to lysosomes. Can you explain the significance of this breakthrough?
Cuong Do (DO): An enzyme called GlcNac-1-phosphotransferase (PTase) is responsible for adding mannose 6-phosphate to the surface of lysosomal enzymes. People have tried and failed for decades to increase the expression of M6P, and everybody gave up. Our co-founder Stuart Kornfeld never gave up. He and his post-doc were able to engineer a variant of PTase that turned out to be 20X more effective than PTase itself in adding M6P to lysosomal enzymes. We built upon this breakthrough to create a platform that is able to create enzyme replacement therapies that have very high M6P content. Furthermore, our gene therapies are the only ones that result in M6P-containing enzymes being produced by the transduced cells.
We expanded upon the innovation and created chimeric antibodies that contain M6P as well. This allows these antibodies (after they bind to the targeted antigens) to be brought to lysosomes in virtually all cells in our bodies for degradation. This is a significant advantage over traditional antibodies relying on Fc clearance by only select immune cells.
CD: You have multiple rare pediatric drug designations and two programs nearing the clinic. What are the most exciting upcoming milestones for your pipeline?
DO: We are preparing to start an Investigator Initiated Trial in Australia for our M021 ERT for Pompe Disease in hopes of obtaining early human data demonstrating M021’s superiority over the standard of care.
CD: How does your lysosomal targeting platform extend beyond rare diseases, particularly in oncology with your chimeric PD-L1 and PD-1 antibodies?
DO: We figured out a way to add M6P to any protein, including antibodies. Our chimeric antibodies can be cleared by virtually all cells in the body since virtually all cells have receptors for M6P. This is especially effective for clearing surface antigens from cell surfaces. Our chimeric PD-L1 antibody is able to clear virtually all PD-L1 from the surface of tumor cells and thus activate T-cells and drive T-cell mediated tumor killing. Our chimeric version of Keytruda is able to remove PD-1 from the surface of T-cells and has shown to be more effective in inhibiting tumor growth in vivo than Keytruda itself.
CD: Can you walk us through your IP position and how it supports your growth strategy?
DO: We have invested heavily in IP that has created a portfolio of 9 patent families, 9 issued patents, and ~20 still in prosecution.
CD: Where are you in your fundraising journey, and what types of investors or partners are you looking to engage with?
DO: We have raised ~$40 million in our Seed and A rounds, which we invested to get our programs to where they are today. We are trying to raise a $5 million bridge now in anticipation of a $50+ million Series B next year. In addition to investors, we want to engage with potential partners who might be interested in our molecules.
CD: How did participating in the Innovator’s Pitch Challenge at RESI Boston help advance your business development or investor connections?
DO: We met a few companies who might be interested in partnering on some of our molecules. We’re continuing the conversations.
IPC Applications are now open for the next Innovator’s Pitch Challenge at RESI London 2025 and RESI JPM 2026, with spots filled on a rolling basis.
By Momo Yamamoto, Senior Investor Research Analyst, LSN
RESI London returns on December 4, 2025, at the King’s Fund, 11 Cavendish Square, as part of the UK’s largest life science partnering and venture week. Organized by Life Science Nation, RESI (Redefining Every Stage of Investment) brings together early-stage life science and healthcare innovators with hundreds of global investors and strategic partners for a full day of partnering, networking, educational content, and exhibits. Virtual partnering will continue on December 8–9, extending the opportunity to build new relationships.
A highlight of every RESI conference is the investor panel programming, where active investors and strategic partners share candid insights with entrepreneurs on what they look for, how they invest, and how startups can best position themselves for success. This year’s London panels will provide in-depth discussions across some of the most dynamic and fast-growing areas of healthcare innovation.
Partnering with Big Pharma
Building Strategic Relationships to Accelerate Innovation
Securing a Big Pharma partnership can be transformative for early-stage companies. Leaders from major pharmaceutical business development and venture teams will share how they evaluate early partnerships, what they seek in collaborators, and how startups can stand out in a competitive field.
Angels & Family Offices
Flexible Capital and Long-Term Support for Early-Stage Innovators
Family offices and angel investors are increasingly active in healthcare, often bringing patient capital and a long-term perspective. Panelists will discuss what differentiates them from institutional investors, the types of opportunities they prioritize, and how founders can approach these funders successfully.
Medical Devices & Diagnostics
Forward Looking Trends in MedTech Innovations
The medtech sector continues to evolve rapidly, with new technologies driving precision care, digital integration, and improved patient outcomes. Investors in this session will share their outlook on the most exciting innovations, challenges to commercialization, and what makes a device or diagnostic investment-ready.
Digital Health & AI
Harnessing Technology to Transform the Patient Journey
Digital health and AI solutions are reshaping care delivery and patient engagement. This panel will highlight what excites investors most in digital platforms, data-driven technologies, and AI applications—and the key factors that determine which companies will succeed in this fast-moving space.
UK / Europe Ecosystem
Global Opportunities in a Dynamic Innovation Landscape
London and the broader UK/European ecosystem offer unique opportunities for entrepreneurs and investors alike. This panel will feature funders with deep experience across these markets, discussing emerging trends, cross-border deal-making, and strategies for startups seeking to expand globally.
Early Stage Therapeutics
Accelerating Breakthrough Therapies in Pre-Clinical and Early Clinical Stages
Developing therapeutics in early clinical phases presents both great promise and high risk. Investors in this session will share how they assess early-stage science, key milestones that de-risk programs, and where they see the next wave of transformative therapies emerging.
Seed Funds
Catalyzing the Earliest Stages of Healthcare Innovation
Seed funds are critical to getting transformative ideas off the ground. This panel will explore how seed-stage investors evaluate opportunities, balance risk and return, and support entrepreneurs through their first fundraising rounds.
Whether you are developing therapeutics, devices, diagnostics, or digital health technologies, the RESI London investor panels offer a rare opportunity to hear directly from the investors shaping the future of healthcare.
New this year: A combi ticket option is available for RESI London + Genesis 2025, giving you access to both partnering events in one streamlined package. Save £300 with Super Early Bird rates available until October 3.
The firm is focused on therapeutics companies and does not invest in medical devices, diagnostics, or digital health. The firm is open to considering assets of very early stages, even those as early as lead optimization phase. The firm considers various modalities, including antibodies, small molecules, and cell therapy. Currently, the firm is not interested in gene therapy. Indication-wise, the firm is most interested in oncology and autoimmune diseases but has recently looked at fibrotic diseases and certain rare diseases as well.
The firm is opportunistic across all subsectors of healthcare. Within MedTech, the firm is most interested in medical devices, artificial intelligence, robotics, and mobile health. The firm is seeking post-prototype innovations that are FDA cleared or are close to receiving clearance. Within therapeutics, the firm is interested in therapeutics for large disease markets such as oncology, neurology, and metabolic diseases. The firm is open to all modalities with a special interest in immunotherapy and cell therapy.
A strategic investment firm of a large global pharmaceutical makes investments ranging from $5 million to $30 million, acting either as a sole investor or within a syndicate. The firm is open to considering therapeutic opportunities globally, but only if the company is pursuing a market opportunity in the USA and is in dialogue with the US FDA.
The firm is currently looking for new investment opportunities in enterprise software, medical devices, and the healthcare IT space. The firm will invest in 510k devices and healthcare IT companies, and it is very opportunistic in terms of indications. In the past, the firm was active in medical device companies developing dental devices, endovascular innovation devices, and women’s health devices.
A venture capital firm founded in 2005 has multiple offices throughout Asia, New York, and San Diego. The firm has closed its fifth fund in 2017 and is currently raising a sixth fund, which the firm is targeting to be the largest fund to date. The firm continues to actively seek investment opportunities across a […]
JPM is creeping up on you once again, and you still don’t have an event planned. All the good venues are gone and all you’re left with are subprime ones or those with sky-high prices. Why not work with us to plan your best event or partnering table rental at the centrally located Marriott Marquis? 
Cuong Do
Next Phase Newsletter 