Partnering conferences are a great place to meet investors, in-licensors and strategic partners. These events tend to be segmented in the following ways:
1) Focus: General, Licensing/BD or Investment
2) Modality: Biotech, Device/Diagnostics, Digital Health
3) Therapeutic area: General or Therapeutic area-specific
4) Stage: General or Early Stage
While it seems obvious, it is critical to align your events (and your limited time and budget) with your company objectives. In my experience at dozens of different partnering conference, I’ve found that each of the above are largely binary. For example, while a Licensing/BD conference will have some investors attending, you’ll have many more meetings with investors at a investment-focused meeting. And vice-versa. Additionally, an interesting pattern that I’ve noticed is when it comes to stage, a partnering event that has a general focus tends to skew late-stage (clinical or later, with lots of players looking for phase 3 or commercial assets). This leaves companies with preclinical or early clinical assets scrambling to identify and meet the relatively few investors who are interested in early-stage companies.
Since partnering conferences allow for a limited number of outgoing meeting requests that can be in the ‘requested’ state, it’s important for you to be able to identify the attending investors that are a good fit for your company. This is complicated by the fact that investors typically don’t do a stellar job populating their profile with information that makes their remit clear. While it may be tempting to use the filters provided by the partnering system to identify best-fit investors, this ONLY works if every investor profile is consistently populated. Why? Because blank values are not returned in filtered searches. What does that mean? That means that if you use the filters in the partnering system to look for those who invest in oncology, and there are some oncology investors who have not filled out their therapeutic area field in their profile, those investors will not be returned in the results. Some partnering conference providers, such as RESI, prevent this issue by having the staff populate the investor profiles on behalf of the investors, ensuring that all profiles are complete and searchable.
All that said, what do you need to look for to find the investors that fit your company best? The most important criteria (that you probably know already if you’ve done any investor outreach) is stage. “Too early” is a response that every pre-clinical and phase 1 company has heard a million times. At RESI it’s easy. You can filter accurately on stage. But at other conferences that depend on the investor to self-populate their profile, you’ll have to read the profile carefully and visit the website. If it doesn’t say explicitly, then look at the portfolio companies.
The next aspect is the assets under management and the check size range. This kind of information not only shows if the investor is appropriate for the amount you’re raising, but also shows if the investor is indeed an investor and not a financial consultancy or investment bank (in some conferences, such entities end up being classified as investors).
Next, and as alluded to above, is the therapeutic area focus. While many investors go across therapeutic areas, some focus on only one or a few.
Next is the modality. Of course if you’re a med tech investor you don’t want to target a biotech-only investor. Within biotech, there are some investors that only do advanced therapies and some who do everything except advanced therapies. Etc.
Next there is the geographic focus. Some investors target specific geographies.
Finally, there is the investor type or model. Not all investors are equity investors. Some are debt, some royalty, some are venture builders, some are CROs that provide services for equity, etc.
If you have access, looking up the investor in Life Science Nation’s investor database will return all the details you need with regard to the above. Other databases have information on investments a given investor made, which provides some insight. By ensuring the investor you send a meeting request to is actually suitable for your company, you’ll maximize your ROI and, with any luck, extend your cash runway.
This week, we provide some lightning takes on recent translational papers that caught our eye. We saw several preclinical advances in approaches for pain, neurodegeneration, cardiovascular disease and bone disorders. In the gene-editing arena, several new large DNA insertion technologies and RNA-targeting CRISPR systems came to the fore.
But before we dive in, we want to highlight theĀ New England Journal of MedicineĀ report from the groups of Rebecca Ahrens-Niklas and Lindsey George at the Childrenās Hospital of Philadelphia that details a neuroepithelial tumor in a 5-year-old boy with severe mucopolysaccharidosis type I (MPSI, a.k.a. Hurler Syndrome) 4 years after receiving an intracisternal injection of an AAV-9 gene therapy.
Summary timeline (A) of a patient with severe Hurler Syndrome who developed a neuroepithelial tumor 4 years after intracisternal administration of AAV-9 delivering an a-L-iduronidase (IDUA) transgene under the control of a cytomegalovirus enhancer and a chicken Ī²-actin promoter (B). Axial and coronal MRI of the patientās head performed 4 years after treatment revealed an intraventricular mass associated with truncated and rearranged AAV vector sequences integrated into intron 4 of the PLAG1 (pleiomorphic adenoma gene-like 1) gene on chromosome 8. Source:Ā NEJMā
Needless to say, approved AAV-based gene therapy products have a long track record of safety, efficacy and long-term transgene expression, but the specter of insertional mutagenesis has always loomed, even though AAV is aĀ predominantly episomalĀ vector. More than five years ago, a paper on hemophilia A dog studies published in Nature Biotechnology reportedĀ 1,741 unique AAV integration eventsĀ in liver and clonal expansions of transduced hepatocytes, with many integrations near growth-related genes. In that case, no tumors were seen. Human liver-biopsy studies after AAV gene therapy have similarly made clear that integration and clonal hepatocyte expansion can happen, while not showing obvious malignant transformation. The NEJM report stands out as providing the first well-documented case of human oncogenesis plausibly linked to AAV vector integration. We can expect it to lead to tighter regulatory and post-marketing oversight of AAV gene therapies, as illustrated by the clinical hold the US Food and Drug Administration (FDA) already placed onĀ RegenxbioāsĀ gene therapy for Hurler, which wasĀ reported back in January. The takeaway for the investment community is that this is not entirely unexpected and should be viewed in the context ofĀ >6,000 patients receiving AAV gene therapy to date without major long-term toxic effects.
Safety signals have also been a recurring theme for drugs targeting sodium voltage channels (Nav1.7) in different pain indications. Multiple industry programs have encounteredĀ problemsĀ with off-target effects and poor clinical translation. Now a team led by Wengsheng Zhang at Sichuan University has identified potent nonopioid analgesics targeting multiple voltage-gated sodium channel isotypes with improved efficacy when tested their efficacy in perioperative rat models (PNAS). We wonder how such a broad approach would mitigate some of the safety flags encountered by previous clinical trials of investigational drugs targeting this pathway. Elsewhere, Xiao-Ming Li and collaborators at Zhejiang University School of Medicine set out to mitigate some of the adverse events of cannabinoid 1 (CB1) agonists, such as reduced locomotion, hypothermia, addiction and analgesic tolerance using so-called biased signaling and targeting downstream signaling cascades mediated predominantly through inhibitory guanine nucleotide binding protein (Gi), rather than beta-arrestin. They show their Gi-biased inhibitors display analgesic properties, but with reduced side effects when tested in mice (Cell). Over recent years, industry has explored cannabinoids to treat a wide range diseases, includingĀ chronic kidney disease,Ā glaucomaĀ and evenĀ obesity, again with limited clinical success. It will be interesting to see whether drugging a downstream signaling pathway will bring greater reward.
While cannabinoids havenāt exactly set the world of company formation alight, platforms leveraging autophagy biology are another story. In the past five years,Ā Lysoway Therapeutics,Ā Retro Biosciences,Ā Casma Therapeutics,Ā Automera Therapeutics,Ā PAQ TherapeuticsĀ andĀ AUTOTAC BioĀ have all received funding for platforms leveraging auto-phagosomal pathways, such asĀ ATTEC,Ā AUTAC,Ā AUTOTAC,Ā chaperone-mediated autophagyĀ orĀ AUTAB. The latest instantiation of ATTEC is described in a paper by Einar Sigurdsson and researchers from New York University, who develop single-domain antibodies to promote autophagy-mediated tau degradation in patient-derived neurons, improving motor function in tauopathy mice (Science Translational Medicine). Autophagy is also the focus for a collaboration between the Jia-Hong Lu team at the University of Macau and MindRank AI, which developed an AI-based screening platform using a variational autoencoder trained on a library (from MedChemExpress and TSBiochem) of over 1 million compounds to identify brain-penetrant small molecule autophagy enhancers effective in mouse models of Alzheimerās disease (Nature Biomedical Engineering).
Elsewhere in the neurodegenerative disease field, TDP-43 aggregation is a hallmark of disorders like amyotrophic lateral sclerosis and frontotemporal dementia.Ā AcurastemĀ andĀ QuralisĀ have been tackling these diseases using antisense oligonucleotides (ASOs) to modulate splice-switching of genes affected by mutant TDP-43. But new research from the groups of James Shorter at the University of Pennsylvania, Christopher Donnelly at the University of Pittsburgh, Nicolas Fawzi at Brown University, Brigid Jensen at Thomas Jefferson University and Jeetain Mittal at Texas A&M reveals that short 34-nucleotide RNAs can act as chaperones to inhibit TDP-43 aggregation and prevent neurodegeneration in the mouse. This potentially opens up short RNA chaperones as a new therapeutic modality for protein-folding disorders (Science).
Moving away from the CNS, some intriguing advances in other therapeutic areas popped into our inbox. One of the new frontiers for oligonucleotide therapies is common cardiovascular indications, such as heart failure and atrial fibrillation. For example, Ionisā transferrin-receptor 1 targeted ASO for downregulating phospholamban in R14-deleted dilated cardiomyopathy justĀ entered phase 1 testingĀ in a development partnership with AstraZeneca. Along these lines, two teams headed by Matthias Nahrendorf and Maarten Hulsman at Harvard Medical School report another target, osteopontin (Spp1), downregulation of which with an antibodyāsiRNA conjugate targeting TREM2+ cardiac macrophages suppresses atrial fibrillation in mice (Nature Cardiovascular Research).
Another area likely to attract more commercial activity going forward is metabolic bone disease.Ā Last December, the US Food and Drug Administration (FDA) made a landmark regulatory shift, formally qualifying percentage change from baseline at 24 months in total hip bone mineral density (BMD) via imaging as a validated surrogate endpoint (previously, bone disease trial times typically took anywhere from two to five years). Two recent papers discuss new therapeutic approaches to heterotopic bone formation after injury. In the first, two teams led by Benjamin Levi and Michael Dellinger from UT Southwestern show that vascular endothelial growth factor D (VEGF-D)-induced lymphangiogenesis can promote heterotopic bone resorption in mice (PNAS). And across the Atlantic, the groups of Johan Keller and Anke Baranowsky at the University Medical Center Hamburg-Eppendorf target extracellular traps from myeloid cells using an FDA-approved recombinant DNAse 1 Pulmozyme to inhibit traumatic heterotopic ossification in mice (Science Translational Medicine; Roche/Genentechās Pulmozyme (dornase alpha) isĀ approved only for the pulmonary indication cystic fibrosis).
Moving onto advanced genetic therapeutics, several advances caught our attention in the gene-editing space. While programmable recombinases/integrases capable of introducing genetic cargoes >10 kb have been prominent in journals, momentum in commercializing these approaches has proceeded at a moderate pace, withĀ Brink Therapeutics,Ā Seamless TherapeuticsĀ andĀ Stylus MedicineĀ all raising funding in the past three years. The ability of recombinases to introduce large constructs has been touted as a key advantage over prime editing, which traditionally can only achieve desired edits no larger than ~300 bp. In this context, three recent papers disclose alternative prime-editing approaches for the genomic insertion of large sequences, overcoming the sequence size limitation. First, research patented by Ying Zhangās group at Wuhan University shows that quadruple paired pegRNAs enable prime editing based genomic insertion of sequences as long as 26 kb in vitro (Nature). Second, the teams of Haoyi Wang, Chenxin Wang and Wei Li at the Chinese Academy of Science developed āPRIME-Inā, a genome editing platform for the integration of up to 3 kb-long DNA sequences in human T cells independent of double-stranded DNA breaks (Nature Biomedical Engineering). Last, the groups of Erik Sontheimer and Wen Xue at the University of Massachusetts Chan Medical School described a āprime assemblyā approach for the insertion of DNA fragments as long as 11 kb (Nature).
Finally, in the area of RNA editing, two recent studies expand the palette of CRISPRāCas effectors capable of targeting and manipulating cells at the level of transcripts rather than nuclear DNA. A paper from I-Ming Hsingās group at Hong Kong University of Science and Technology describes the first use of DNA-guided CRISPRāCas12a effectors for programmable RNA recognition and cleavage (Nature Biotechnology). In a second paper, Yang Liuās team at the University of Utah, Chase Bieselās group at University of WĆ¼rzburg and scientists fromĀ Akribion TherapeuticsĀ and BRAIN Biotech engineer CRISPRāCas12a2 for the selective, DNA-triggered killing of virally infected human cells on the basis of their transcriptional profile (Nature).
Conference roundup
Selected startups raising funds in past three years presenting data at the American Society for Cell and Gene Therapy (ASCGT), Boston,Ā May 11ā15.
If youāre interested in commercializing your science,Ā get in touch. We can help you figure out the next steps for your startupās translational research program and connect you with the right investor. Follow us on X, BlueSky and LinkedIn. Please send feedback; weād love to hear from you (info@haystacksci.com).
As partnering activity ramps up ahead of convention week in San Diego, early-stage life science companies are preparing for a critical week of fundraising, licensing, and strategic business development. To help companies better understand how large pharmaceutical companies evaluate new opportunities, Life Science Nation is hosting a webinar featuring leaders from Merck, Servier, and Meiji Pharma USA.
The webinar, Large Pharma BD & Investment: Merck, Servier & Meiji Pharma Prep You for RESI & Convention, will take place on June 2, 2026 at 1:00 PM ET and will be moderated by Sougato Das.
Carla BauerDirector, Search and Evaluation, BD & Licensing Merck
Irene Blat, PhDHead of External Innovation, NA Servier
Sho TakahataSenior Director, Venture Investment Meiji Pharma USA
The discussion will explore how pharma companies source and evaluate external innovation, what teams look for during initial meetings, how internal screening processes work, and what makes a company stand out for continued engagement. Topics will also include licensing, R&D partnerships, strategic investment, platform collaborations, and practical tips for improving partnering conversations during convention week.
For companies preparing for RESI San Diego and broader convention week activity, the webinar offers an opportunity to hear directly from pharma business development and investment leaders before arriving in San Diego.
RESI San Diego begins June 22 with an in-person conference day followed by four days of virtual partnering on June 23ā24 and June 29ā30, connecting early-stage companies with active investors, pharma scouts, strategic partners, and global healthcare stakeholders.
After securing 1st Place in the Innovatorās Pitch Challenge at RESI Europe, StimOxyGen is gaining momentum as it advances its lead program, SGEN-33, toward clinical development. In this interview, Sian Farrell discusses the science behind the platform, upcoming milestones, and how the RESI experience has accelerated investor engagement.
Caitlin Dolegowski (CD): For those new to StimOxyGen, how would you describe SGEN-33 and the problem it is solving in a way that resonates with investors?
Sian Farrell (SF): SGEN-33 is a pH-responsive, oxygen-generating nanoparticle designed to overcome tumour hypoxia, one of the biggest barriers limiting the effectiveness of radiotherapy and other cancer treatments. Many aggressive solid tumours, particularly pancreatic cancer, are severely oxygen deprived, making them highly resistant to therapy. SGEN-33 selectively activates within the acidic tumour microenvironment, releasing oxygen directly where it is needed to help re-sensitise tumours to treatment. What makes the opportunity particularly compelling is that we are addressing a fundamental biological resistance mechanism that impacts multiple high-value oncology indications. Rather than replacing existing therapies, SGEN-33 is designed to enhance them, positioning StimOxyGen within the growing combination of therapy landscape.
CD: What makes this approach particularly compelling from a commercial and clinical perspective compared to existing strategies?
SF: Clinically, our approach is differentiated because SGEN-33 generates oxygen directly within the tumour microenvironment rather than relying on systemic oxygen delivery methods, which have historically shown limited success. Existing hypoxia-targeting strategies such as hyperbaric oxygen therapy or intratumoural injections face significant limitations in practicality, scalability, or clinical adoption. In contrast, SGEN-33 is designed for intravenous administration and tumour-selective activation, offering a scalable and clinically feasible solution. Commercially, we believe this creates a highly attractive platform opportunity. Radiotherapy is used in approximately 60% of cancer patients worldwide, yet hypoxia remains a major unresolved challenge. By integrating into existing standards of care, SGEN-33 has the potential to enhance multiple treatment modalities across several solid tumour types without requiring clinicians to completely change current workflows. Importantly, we have already demonstrated strong preclinical efficacy and safety data in highly hypoxic tumour models, including pancreatic cancer, triple-negative breast cancer, and aggressive prostate cancer. Our studies have shown significant tumour growth reduction and survival benefit when SGEN-33 is combined with radiotherapy.
CD: What key milestones or inflection points should investors be watching as you move toward clinical development?
SF: The next 18ā24 months represent a highly important period for StimOxyGen as we advance SGEN-33 toward clinical development. Our current focus is on completing key IND-enabling activities, including GLP toxicology and DMPK studies, GMP manufacturing scale-up, FDA regulatory engagement, and expansion of our radiotherapy-immunotherapy datasets. Alongside these milestones, we are progressing collaborations with leading translational oncology centres including Memorial Sloan Kettering Cancer Center (MSK), advancing early clinical strategy and trial design activities, and continuing to strengthen our scientific and clinical advisory network. A particularly exciting area is the growing evidence of immune-mediated effects observed in our preclinical studies, which may create future opportunities in combination with immunotherapy approaches.
CD: What are your current fundraising priorities, and what types of investors or partners are you looking to engage at this stage?
SF: We are currently raising $7.5 million to advance SGEN-33 through IND-enabling development and position the programme for First-in-Human clinical studies, with a target close by Q1 2027. The financing will support key value-creation milestones including GLP toxicology, DMPK studies, GMP manufacturing scale-up, FDA regulatory engagement, and continued expansion of our radiotherapy-immunotherapy datasets. In parallel, we are progressing clinical strategy and early trial design activities through collaborations with leading translational oncology centres, including Memorial Sloan Kettering Cancer Center (MSK). We are particularly interested in engaging with specialist life science investors, oncology-focused funds, and strategic partners with expertise in radiotherapy, immuno-oncology, nanomedicine, and translational drug development.
CD: How did participating in RESI Europe and the Innovatorās Pitch Challenge impact your visibility and conversations with investors?
SF: Participating in RESI Europe was hugely valuable for StimOxyGen from both a networking and visibility perspective. Having the conference based in Lisbon created an important opportunity to expand beyond the UK ecosystem and connect more directly with the broader European life science investment community. It allowed us to significantly grow our investor network and establish new relationships with international investors and strategic partners. Winning 1st Place in the Innovatorās Pitch Challenge increased our visibility and credibility within the global biotech community and created strong momentum in investor conversations. An additional benefit is the opportunity to attend future RESI conferences, including events in the United States, which will help us continue expanding our US investor and strategic partner network as we move toward clinical development. Beyond the exposure itself, the experience also provided a significant confidence boost for our team and reinforced that the work we are doing is resonating internationally.
CD: What stood out most about the Innovatorās Pitch Challenge experience compared to other pitch opportunities?
SF: What stood out most was the quality and relevance of the audience. Iāve participated in pitch competitions previously, but many were more sector-agnostic and included a broad mix of industries and technologies. At RESI, it was particularly meaningful to receive recognition in a highly relevant and competitive life sciences environment, surrounded by innovative biotech and healthcare companies tackling major clinical challenges. The discussions also felt far more relationship-driven than transactional. Conversations extended beyond the pitch itself and focused on clinical strategy, regulatory pathways, commercialization, and long-term value creation. Importantly, the support from the Life Science Nation (LSN) team did not feel like a āone-and-doneā experience. The ongoing opportunities through future RESI events and the wider LSN network create continued momentum and provide a strong platform for us to further expand our international investor and strategic partner network moving forward.
CD: Following your win, what are the next key priorities for StimOxyGen as you move into your next phase of growth?
SF: Our biggest priority is maintaining the momentum we have built over the past 18 months as we advance SGEN-33 toward clinical development. Since completing our first VC financing round in January 2025, we have continued to de-risk the technology, expand our international investor network, progress collaborations with Memorial Sloan Kettering Cancer Center (MSK), and strengthen our translational and regulatory strategy. Winning the RESI Europe Innovatorās Pitch Challenge was another important milestone that reinforced the growing momentum around the company. Over the next phase of growth, our focus is on advancing SGEN-33 through IND-enabling development, progressing FDA engagement, scaling manufacturing capabilities, and continuing to strengthen our clinical strategy. Of course, securing the capital required to move the programme into the clinic remains a critical priority. We believe StimOxyGen is at a genuinely exciting inflection point, and we are actively looking to partner with investors who share both our ambition and our sense of urgency. At the heart of everything we do is the patient. We are working on therapies for people facing some of the most difficult-to-treat cancers, where treatment options are limited and outcomes remain devastatingly poor. That reality keeps our team focused every day and drives our determination to move as quickly and responsibly as possible toward the clinic. For us, this is about far more than building a company ā it is about giving patients and families hope where too often there currently is very little. And, if our story resonates with you, we would love to continue the conversation.
Additional Innovatorās Pitch Challenge (IPC) slots are now available, giving companies the opportunity to pitch directly to investors, receive live feedback, and boost visibility ahead of the event. Applications close May 22.
The fourth week of June is one of the largest gatherings of life science business development and investment professionals on the calendar, second only to JPM. If you are an early-stage company raising anywhere from $250K to $75M, that week in San Diego is not optional. The question most founders are asking right now is whether attending RESI means missing BIO.
The short answer is no. Here is why.
RESI partnering starts early morning on June 22. BIO Convention partnering does not start until early afternoon. That means you can run a full morning of investor meetings at RESI before BIO gets going. The two venues are about 15 minutes apart, making it straightforward to move between them in the afternoon. RESI has virtual days both that week and the following week, so any meetings that do not fit in person can be held on Zoom with no schedule conflicts.
If you find yourself double booked across both events on Monday afternoon, the partnering systems give you real options. Move the Convention meeting to another day. Move the RESI meeting to the morning or to a virtual slot. Or simply decide which meeting matters more for your specific raise. Having choices is better than not having them.
Fundraising is a numbers game. Companies with tight budgets need to maximize every hour and dollar spent in San Diego each week. RESI is not a scheduling conflict. It is more meetings with investors and pharma external innovation teams that are specifically focused on early-stage deals. Add it to your agenda.
Bonus: Increase your networking ROI by attending the many side events and receptions during Convention week. Luckily we’ve assembled the most complete list for you! Click here.
An old adage in drug development states that any successful program for an advanced medicine must overcome three central challenges: first, delivery; second, delivery, and third ā¦ delivery! Lipid nanoparticle (LNP) technology andĀ N-acetyl galactosamine-(GalNAc) conjugates have opened the liver to a wide range of genetic medicines, and transferrin 1 receptor (TfR1) conjugates are beginning to access the CNS via intravenous delivery with brain-shuttle technology. But tissues like the lung, kidney, muscle and heart remain very much a work in progress.
In the pulmonary space, a small cadre of companies are pursuing inhaled LNP delivery technologies.Ā Recode Therapeutics,Ā Vertex PharmaceuticalsĀ andĀ ArcturusĀ are the main players, while other firms such asĀ 4DMTĀ andĀ Krystal BiotechĀ are focusing on viral gene therapies for lung delivery.
Just a few days ago, one of these LNP programsĀ got the chop. The Vertex/Moderna phase 1/2 study of VX-522, an aerosolized LNP to deliver mRNA encoding full-length cystic fibrosis transmembrane conductance regulator (CFTR) to the lungs of cystic fibrosis patients, which had been paused due to tolerability issues, is now permanently discontinued. According toĀ reports, the Moderna LNP was the culprit, leading to lung inflammation. That leaves Recode and Arcturus as the frontrunners, a rather small field, given the entire market opportunity for a pulmonary delivery solution. All told, in 2023, there wereĀ 569.2 million casesĀ of chronic respiratory diseases and 4.2 million deaths from respiratory disease.
Recode now isĀ enrolling patients into the phase 2 trialĀ of its Selective Organ Targeting (SORT), LNP platform (RCT2100) that delivers an mRNA encoding CFTR in combination with the small-molecule CFTR potentiator ivacaftor (theĀ SORT technologyĀ was originallyĀ licensed outĀ of Daniel Siegwartās group at UT Southwestern). The other LNP platform, Arcturusā LUNAR LNP technology, also has encouragingĀ interim dataĀ from its phase 2 trial in cystic fibrosis patients and from itsĀ programĀ delivering ornithine transcarbamylase mRNA.
These LNPs (and most other LNP delivery platforms) are built around the same four common components: an amino ionizable lipid, a helper lipid, a polyethylene glycol lipid and cholesterol. The formulations follow this scheme but with different combinations of proprietary lipid forms; thus, in Arcturusā LUNAR LNP, distearoylphosphatidylcholine (DSPC) performs the helper lipid function, whereas in Recodeās SORT LNP, it is 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Overall, however, just a handful of novel lipid components have gone into humans so far.
According to Siegwart, the field is in dire need of developing a broader palette of cationic lipids that are both efficient and non-toxic for the pulmonary epithelium; ultimately, the goal would be a delivery technology capable of targeting specific cell types in the lung (with many new cell subtypes continuing to beĀ identified).
The respiratory epithelium contains a diverse set of cell subtypes important in maintaining respiratory homeostasis. Dysfunction in these cells can lead to disease. PNEC, pulmonary neuroendocrine cell; PCD, primary ciliary dyskinesias; CGRP, calcitonin gene related peptide; SIDS, sudden infant death syndrome; SCLC, small cell lung carcinoma; Mtb, Mycobacterium tuberculosis; COPD, chronic obstructive pulmonary disease. Source:Ā Mucosal Immunologyā
In a recent article inĀ Nature Biomedical Engineering,Ā Siegwart and his group at UT Southwestern introduce the design and evaluation of a new class of lung-targeting (LuT) lipids that enable the highly efficient and selective delivery of mRNA and CRISPRāCas9 gene-editing systems to the lungs.
They synthesized and screened a library of 444 lipids using a combinatorial approach, systematically varying amine head groups and hydrophobic tails. Through in vivo testing and structureāactivity relationship analysis, they identified key features in the lipids that most effectively targeted the lung: a distinctive ātripod-likeā structure, consisting of a quaternary amine head, three long alkyl chains and a short fourth chain.
Design, synthesis and multi-round evaluation of LuT lipids for pulmonary delivery.Ā a, LuT lipids were chemically synthesized by one-step combinatorial conjugation of diverse amine heads and alkyl/alkenyl bromide tails, formulated into LuT LNPs and intravenously administrated into mice for in vivo evaluation. SARs governing the function of LuT LNPs were carefully analyzed.Ā b, After in vivo evaluation, the top-performing LuT lipids with a tripod-like structure were identified and showed exceptional mRNA delivery efficiency, which inspired the in-depth investigation into their performance in specific cell type targeting, mechanisms and gene editing. Source:Ā Nature Biomedical Engineeringā
Compared to benchmark formulations, the best-performing LuT-containing LNPs achieved up to a 25.5-fold increase in mRNA delivery and a 9.2-fold improvement in gene-editing efficiency, with >90% of delivery localized to the lungs. These LuT-LNPs successfully transfected multiple lung cell types, including endothelial, epithelial and immune cells, with some formulations showing preferences for specific cell populations.
Mechanistically, the improved performance was attributable to two main factors. First, the tripod-like structure of lipids promoted endosomal escape by facilitating membrane fusion and LNP disassembly, allowing efficient release of genetic cargo into cells. Second, LuT LNPs formed distinct protein coronas in the bloodstream, particularly enriching for vitronectin, a protein that enhances targeting to lung cells via receptor-mediated uptake.
Siegwart and his team went on to show the therapeutic potential of LuT LNPs. The lead formulation, 1A7B13, enabled effective delivery of IL-10 mRNA in a mouse model of acute lung injury and achieved robust CRISPRāCas9 gene editing in lung tissue. The LNPs showed minimal toxicity and no significant adverse effects in vivo.
This research establishes clear design principles for lung-targeting LNPs and markedly expands the available toolkit for pulmonary gene delivery. It is just the beginning of the translational path, however.
The Siegwart LuT-LNPs must home through the vasculature to the lungs after being delivered intravenously. This is very different from the aerosolized LNP delivery approaches of Recode and Arcturus currently in clinical testing. There may be a case to be made that some pulmonary vascular disease, lung endothelial targets, lung fibrosis, immune-cell or vascular-compartment targets might warrant the intravenous route, but aerosolized LNP delivery provides lower systemic exposure (and thus higher therapeutic index), is more patient-friendly, and rapidly/directly reaches the airway lumen.
Regardless of the route of administration, the translational challenges associated with targeting the lung remain very difficult. In terms of testing formulations in different models, anatomical differences between mouse, ferret and human airways, including physiological size and branching complexity, impact LNP design and aerosol physics.The formulations used for mice may simply not work for people because of differences in cell composition, and lung epithelial and endothelial membranes and āsurfaceomesā. As humans age and develop disease, cell protein and lipid composition may also change, requiring further optimization of LNP formulations. Mice have more narrow airways and faster breathing rates than humans, requiring smaller diameter aerosol droplets (often <2 Āµm) to ensure particles bypass the upper respiratory tract and reach the alveolar regions.
Moreover, humans have ~23 branches in their airways, whereas mice have only 13, meaning an aerosol optimized for a ādeepā reach in a mouse might only reach mid-level bronchi in a human. Furthermore, ferrets are not a widely available model system to study the biodistribution and efficacy of LNPs. Indeed, there are just a few labs in the United States that upkeep ferret colonies.
Last, a human lung’s surface area (~70 mĀ²) isĀ nearly 8.500 timesĀ larger than a mouse’s (~82 cmĀ²), and human tidal volume isĀ roughly 6,000 times greater. This requires significant dose scaling and affects how ādilutedā the LNPs become once they deposit.
Designing in vitro and in vivo systems representative of human biology and capable of predicting LNP biodistribution is also a tall order (especially with such a small cadre of companies working on the problem). For small molecules, the measurement of efficacy in human basal epithelium-derived patient cells carrying a mutation of interest by and large will translate into what you see in the clinic. The pharmaceutical industry has amassed a lot of data to bolster pharmacology.
Unfortunately, that correlation doesnāt necessarily hold for genetic modalities like mRNA or CRISPR/Cas9 constructs. For these medicines, it is very hard to figure out PK/PD. And so, the translation from preclinical work to the clinic can be tricky for an inhaled LNP technology delivering mRNA. It is difficult to really know the degree of protein expression from an inhaled LNP genetic medicine intracellularly without doing a bronchial biopsy (which is of course highly intrusive). And if you need to test your LNP in patients via biopsy, clinicians historically have been very resistant to carrying out such procedures, particularly in very sick patients like some of people with cystic fibrosis who carry nonsense mutations in CFTR. Thus, there is a need for alternative approaches. Certainly, there is an opportunity for more work on organoids or simpler patient cell-derived assays: 2D or 3D alternatives to large animal models like the ferret.
What is clear is that there are enough patients worldwide living with lung disease that further research in this area needs to be encouraged. In this respect, the findings from Siegwartās group are a step in the right direction, with broad implications for treating lung diseases by enabling safer and more precise delivery of RNA-based therapeutics and genome-editing technologies.
Following its recognition as a winner of the Innovatorās Pitch Challenge at RESI Europe, You2Yourself is advancingĀ a new approachĀ to early disease detection through longitudinal biomarker monitoring. In this interview, Bram De Moor discusses the science behind URIMON, the companyās commercialization strategy, and how RESI has supported its investor engagement.Ā
Bram De Moor Founder & General Manager, You2Yourself
Caitlin Dolegowski (CD): For those new to You2Yourself, how would you describe URIMON and the value of longitudinal biomarker monitoring in a way that resonates with investors?
Bram De Moor (BD): URIMON is a personalized, non-invasive, urine-based liquid biopsy platform that uses urinary miRNA profiling to detect multiple serious diseases ā including prostate cancer, lung cancer, and cardiovascular disease ā before symptoms appear. One urine sample generates simultaneous risk scores across multiple conditions.
The longitudinal dimension is key: repeated monitoring detects biological drift months to years before clinical symptoms ā the difference between catching cancer at stage I versus stage III. With no needles, no clinic visit, and at-home collection with mail-in capability, URIMON is designed for scalable, population-level adoption.
CD: What makes your approach to early disease detection fundamentally different from traditional diagnostic models?
BD: Traditional diagnostics are reactive and often focus on a single biomarker. URIMON differs in three key ways:
Multi-disease detection from a single sample, analyzing hundreds of miRNA species simultaneously
Focus on molecular signals rather than anatomical changes, enabling earlier detection
Use of urine as a scalable, patient-friendly biofluid that captures signals from across the body
This approach provides a unified molecular health view, reducing fragmentation across specialties.
CD: You have built a unique biobank of longitudinal samples ā how does this dataset strengthen your technology and create a competitive advantage?
BD: The URIMON Biobank, developed since 2019 with over 6,500 participants under IRB-approved and GDPR-compliant protocols, is a significant strategic moat.
It enables algorithm training on longitudinal patient data, including individuals who later develop disease, supporting prospective validation. It also ensures robustness across cohorts, allowing classifiers to generalize beyond a single institution.
Replicating this dataset would require years and substantial capital, making it a durable barrier to entry.
CD: How do you think about commercialization, particularly your subscription-based model and the path toward broader reimbursement and population-level adoption?
BD: Our strategy is staged to de-risk scaling. We are entering the market under the EU IVDR Article 5(5) in-house LDT framework to accelerate time to revenue.
Our subscription model (ā¬299ā499/year) targets individuals, employer groups, and occupational health programs, aligning recurring revenue with longitudinal monitoring.
Reimbursement will follow through HTA submissions in Europe, with FDA De Novo clearance as a parallel pathway in the U.S.
CD: What key milestones or inflection points should investors be watching as you move toward your planned 2027 market entry?
BD: Key milestones include:
Clinical validation and publication of performance data
Regulatory progress under IVDR and FDA pathways
Launch of commercial infrastructure and first paying customers
Strategic partnerships and completion of financing rounds
These milestones will demonstrate both technical validation and commercial traction.
CD: How did participating in RESI Europe and the Innovatorās Pitch Challenge impact your investor visibility and strategic conversations?
BD: RESI provided direct access to European and transatlantic investors actively seeking early-stage diagnostic companies ā a highly targeted audience that is difficult to reach through traditional outreach.
The Innovatorās Pitch Challenge offered structured validation in a competitive setting, signaling credibility to institutional investors. It also led to new investor conversations and follow-up meetings now underway.
CD: Following your recognition at RESI Europe, what are the next key priorities for You2Yourself as you move into your next phase of growth?
BD: Our focus over the next 12ā18 months includes:
Expanding clinical evidence through continued biobank growth and prospective studies
Securing financing through grants and a seed-to-Series A bridge round
Scaling team and infrastructure across lab, regulatory, and business development functions
With favorable market conditions ā including advances in NGS, growing demand for preventive health, and regulatory clarity ā You2Yourself is well positioned to lead in this space.
Applications are now open for upcoming Innovatorās Pitch Challenges. Companies can apply to pitch at RESI San Diego 2026 and take the stage in front of a global network of investors and partners.
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