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.
By Dennis Ford, Founder & CEO, Life Science Nation (LSN)
As part of Life Science Nation’s series on converting scientific innovation into investable signal, the final layer of the De-Risk Stack addresses exit risk. (Explore the full series here) After market, technical, regulatory, execution, economic, and financing risks are reduced, the final question becomes clear: how does this become a return?
Exit Risk
From Story to Outcome
At the top of the stack is the question every investor ultimately asks: how does this become a return?
Exit risk is not about predicting a specific transaction. It is about defining a realistic, evidence-based path to liquidity. Without that, even well-executed companies remain difficult to fund across multiple rounds.
This begins with clarity on the most likely exit path, acquisition, licensing, or public markets, aligned with the type of company you are building and the norms of your sector.
From there, you must be able to name a credible buyer universe: specific pharmaceutical, biotechnology, device, or platform companies for whom your asset would represent strategic value. Strategic fit explains why those buyers should care, how your product fills a pipeline gap, extends an existing franchise, enables a new modality, or provides differentiated access to a market.
Timing and value inflection points determine when the asset becomes relevant to those buyers. Clinical data, regulatory milestones, partnership signals, and early commercial traction all influence when interest peaks.
Competitive positioning answers why your asset would be selected over alternatives. Deal structure reality grounds expectations in how transactions are done in your space, including licensing terms, milestones, royalties, and acquisition patterns.
Finally, return potential must align with the expectations of the capital investing in the company. A good company is not always a good investment. The scale and timing of the likely outcome must match the risk and capital required to get there.
Exit risk is resolved when the company presents a credible path from development to liquidity, with clear buyers, clear triggers, and realistic structures.
Core Elements of Exit Risk
Exit path clarity
Buyer universe
Strategic fit
Timing
Value inflection points
Competitive positioning
Deal structure reality
Return potential
Sequence and Progression
These risks do not resolve independently. The order in which they are addressed determines outcome.
When this sequence is followed, uncertainty is reduced efficiently and value compounds. When it is not, capital is consumed without progress and even strong assets can stall.
From Risk to Signal
The purpose of de-risking is to generate signal.
Investors do not fund ideas; they fund signal, coherent, cross-validated evidence that enough uncertainty has been removed to justify action. Each layer of the stack produces a different class of signal: market signal, technical signal, regulatory signal, execution signal, economic signal, financing signal, exit signal. As these accumulate and align, an opportunity becomes not just understandable, but investable.
Fundraising, in this view, is not persuasion. It is the systematic production and communication of signal.
Implications
For founders, progress is defined by the reduction of uncertainty, not by the volume of activity or the length of the roadmap.
For investors, the De-Risk Stack provides a structured framework for evaluation, what is resolved, what remains unresolved, and what must be proven next.
For ecosystems, it highlights the missing infrastructure between innovation and capital: shared standards, de-risking platforms, and operating systems that help assets move through this process more reliably.
From Framework to System
The De-Risk Stack defines how life science companies become investable. Implementation defines how that process is executed.
At the company level, this means shaping opportunities deliberately, targeting specific layers of risk, executing against clear milestones, and running structured fundraising campaigns.
At the ecosystem level, it means building infrastructure that can systematically identify, assess, and advance assets through the stack, so promising technologies do not stall for avoidable reasons.
When applied consistently, the De-Risk Stack becomes more than a framework. It becomes a system for converting scientific innovation into investable opportunity.
Closing
The challenge in life science is not discovery. It is the disciplined conversion of discovery into investable signal.
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 … delivery! Lipid nanoparticle (LNP) technology and 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. Recode Therapeutics, Vertex Pharmaceuticals and Arcturus are the main players, while other firms such as 4DMT and Krystal Biotech are focusing on viral gene therapies for lung delivery.
Just a few days ago, one of these LNP programs 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 to 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 were 569.2 million cases of chronic respiratory diseases and 4.2 million deaths from respiratory disease.
Recode now is enrolling patients into the phase 2 trial of its Selective Organ Targeting (SORT), LNP platform (RCT2100) that delivers an mRNA encoding CFTR in combination with the small-molecule CFTR potentiator ivacaftor (the SORT technology was originally licensed out of Daniel Siegwart’s group at UT Southwestern). The other LNP platform, Arcturus’ LUNAR LNP technology, also has encouraging interim data from its phase 2 trial in cystic fibrosis patients and from its program 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 Arcturus’ LUNAR LNP, distearoylphosphatidylcholine (DSPC) performs the helper lipid function, whereas in Recode’s 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 be 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: Mucosal Immunology
In a recent article in Nature Biomedical Engineering, 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 CRISPR–Cas9 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 structure–activity relationship analysis, they identified key features in the lipids that most effectively targeted the lung: a distinctive ‘tripod-like’ 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. 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. 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: Nature Biomedical Engineering
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 CRISPR–Cas9 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 “surfaceomes”. 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 µm) 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 ‘deep’ 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 m²) is nearly 8.500 times larger than a mouse’s (~82 cm²), and human tidal volume is roughly 6,000 times greater. This requires significant dose scaling and affects how ‘diluted’ 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 doesn’t 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 Siegwart’s 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.
Anearly-stage venture capital firm based in the United States is focused on backing transformative healthcare technologies. The firm primarily invests at the pre-Seed stage, supporting companies at formation and early product development. The firm deploys capital from a dedicated early-stage fund and partners with both individual and institutional investors aligned with its focus on innovation and long-term value creation. While the firm invests in U.S.-incorporated companies, it actively supports globally distributed teams and engages with founders across multiple regions.
The firm specializes in health-focused deep technology, with a primary emphasis on neurotechnology and adjacent medical device innovation. The firm invests in companies developing technologies that diagnose, treat, or enhance human health through brain-centered or neurological approaches. Areas of interest include neurotechnology platforms, medical devices, diagnostics, and enabling technologies at the intersection of science, healthcare, and engineering. In addition to its core neurotech focus, the firm also evaluates broader medtech opportunities with the potential to deliver scalable impact across healthcare systems.
From a company and management team perspective, the firm partners with mission-driven founders who combine technical depth with a patient-centered approach to innovation. The firm prioritizes teams developing differentiated technologies with strong scientific foundations, clear clinical relevance, and the potential for global impact. The firm engages closely with founders from the earliest stages, providing strategic guidance, long-term perspective, and support in building durable, high-impact companies.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
The firm is a multi-family office investment and wealth management platform that combines traditional advisory services with direct investment and co-investment opportunities. The firm allocates capital across both direct company investments and third-party funds, providing exposure to high-growth sectors. The firm operates across Europe and the United States and maintains a flexible investment approach spanning multiple asset classes and stages.
The firm has an active focus on health technology and life sciences, including precision medicine, biotechnology, and select medical technology opportunities. The firm evaluates both companies and funds across early-stage and growth-stage investments, with an emphasis on scientific and clinical innovation that can drive meaningful long-term impact. Areas of interest include personalized healthcare, advanced therapeutic modalities, and technologies that improve diagnosis, treatment, and patient outcomes.
From a company and management team perspective, the firm partners with teams demonstrating strong domain expertise, execution capability, and strategic clarity. The firm prioritizes opportunities with robust scientific or technical foundations and credible pathways through development, regulatory processes, and commercialization. The firm invests as a collaborative partner, offering capital alongside strategic insight, co-investment flexibility, and access to a broader network of investors and industry relationships.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
A healthcare-focused venture capital firm with a team grounded in biomedical training and industry experience manages both local currency and USD-denominated funds and invests across early and growth stages. The firm has an established track record of investing in companies across multiple financing rounds and geographies, including Asia, North America, and Europe. The firm maintains a strong conviction in long-term growth opportunities within the global healthcare sector, particularly in cross-border innovation.
The firm invests broadly across therapeutics, medical devices, diagnostics, healthcare IT, and medical services. Within therapeutics, the firm has invested across a range of indications such as oncology, infectious diseases, and autoimmune disorders, covering multiple modalities including small molecules, biologics, and gene-based therapies. The firm also evaluates device and imaging technologies, as well as opportunities in bioinformatics, research tools, and adjacent areas such as animal health. Therapeutic investments typically begin at preclinical stages, while device investments are often made prior to commercialization.
From a company and management team perspective, the firm does not impose strict requirements and remains open to partnering with a wide range of teams and opportunities.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
The firm is a life sciences-focused venture capital firm with a global presence and a track record of investing across private and public markets. The firm manages multiple funds backed by institutional and strategic investors and has built a diversified portfolio of companies, including a meaningful number of seed and incubated ventures. The investment team brings extensive experience across venture investing, biopharmaceutical development, academia, and regulatory environments. The firm operates globally with team members based across key innovation hubs in North America and Asia.
The firm invests across the life sciences sector, targeting areas of high unmet medical need. The firm is flexible across geographies and development stages, leveraging a cross-functional platform to support value creation from early company formation through later-stage and public market investing.
From a company and management team perspective, the firm prefers to lead investments and typically takes board representation. The firm plays an active role in supporting portfolio companies through strategic guidance across capital markets, business development, clinical strategy, regulatory planning, and commercialization. The firm seeks to partner with management teams that demonstrate strong capability, commitment, and the ability to advance innovative technologies.
If you are interested in more information about this investor and other investors tracked by LSN, please email salescore@lifesciencenation.com.
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