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StimOxyGen on Advancing SGEN-33 Following First Place Win at RESI Europe 

12 May

After securing 1st Place in the Innovator’s 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.

Sian Farrell
CEO, StimOxyGen
 Caitlin Dolegowski
Program Director, LSN

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 18–24 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 Innovator’s 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 Innovator’s 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 Innovator’s Pitch Challenge experience compared to other pitch opportunities?

SF: What stood out most was the quality and relevance of the audience. I’ve 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 “one-and-done” 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 Innovator’s 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 — 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 Innovator’s 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.

Apply to Pitch at RESI San Diego

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Do RESI San Diego and BIO Overlap?

12 May

By Sougato Das, President and COO, LSN

Sougato-Das

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.

Register for RESI San Diego

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The Needle Issue #26

12 May
Juan-Carlos-Lopez
Juan Carlos Lopez		 Andy-Marshall
Andy Marshall

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).

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.

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.

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Convention Week: How to Get the Most Investor/Inlicensor Meetings & Exposure 

5 May

By Sougato Das, President and COO, LSN

Sougato-Das

Prep for the June mega-events in San Diego, BIO Convention and the neighboring RESI, starts now. We’re 7 weeks out and it’s getting warm. In another week, the Heat is On by Glen Frey. Three weeks or so after that, scheduling starts and it’s Hot Hot Hot by Buster Poindexter. Finally, when partnering starts on June 22, it’s the Heat of the Moment by Asia. 80s music references aside, here are the top things you need to do NOW to ensure your company succeeds:

  1. Register. Want to meet investors funding seed through series B and pharma external innovation? There will be over 300 at RESI. Click here to take advantage of RESI early bird rates.
  2. Consider registering to pitch, with many opportunities throughout Convention week. Pitching at RESI puts you in front of a panel of well-aligned investors who are obligated to be interactive and give you feedback.
  3. Log into the partnering system and find your ideal partners. Repeat this every week to account for new registrants. At RESI this is straightforward as the LSN staff populates investors profiles very granularly based on the LSN Investor Database. Investors are carefully vetted. Searching for investors interested in a given modality, disease, geography, stage, etc. is fast. Searching for well-aligned partners in the larger Convention ecosystem can require more oversight (e.g. is an in-licensor looking for early stage, late stage or on-market assets?) Join my webinar to learn the best way to do this!
  4. Open as much availability on your calendar/agenda as possible. Convention week is NOT the time to block the early morning time slots because you want to sleep in 😉
  5. Send customized meeting requests. Meetings are more likely to be accepted if you spend some effort customizing each meeting request to the interests of the receiving company. Join my webinar to learn the best way to do this!
  6. Minimize the number of people from your company who are required to attend the meeting. The fewer people in the meeting the more likely it is to get scheduled (if it’s accepted).
  7. Follow-up on unanswered meeting requests. As someone who’s been behind the scenes running partnering at dozens of partnering events, I can tell you there is a complex series of variables that determines if your meeting request gets accepted. Sometimes it’s as simple as the person who would accept your meeting request did not register until later, even though his/her colleagues registered earlier. That’s why it’s important not let unanswered meeting requests languish indefinitely. Join my webinar to learn the best way to do this!
  8. Cancel ‘dead’ unanswered meeting requests. When you determine you won’t get a response for a given meeting request, cancel it to increase your meeting request allotment. Join my webinar to learn the best way to do this!
  9. When scheduling starts, immediately reach out to the other party for meetings that cannot be scheduled due to lack of mutual availability. You can also try reaching out to the partnering system administrators to see if they can help.
  10. Practice your meeting presentation to ensure everything gets finished in the allotted time. For Convention, 25 minutes is a good guide, as meetings can be far apart from each other. For RESI, 30 minutes as meetings are physically close together. To get between RESI and Convention, plan at least 20 minutes.
  11. Take advantage of virtual partnering. RESI provides virtual partnering during Convention week and the following week. Extend your ROI by continuing the momentum of Convention week into the next week.
  12. Be prompt about your follow-up the week after Convention.

Whew! I’m So Tired (by the Beatles) just writing this, I can’t imagine how I feel after I go through the Convention Week + RESI gauntlet! For more details on how to succeed at Convention & RESI, join my webinar on May 20 for all the best tips and tricks!

Sign Up the Webinar

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Reception & Event List for Convention Week in San Diego

21 Apr

By Sougato Das, President and COO, LSN

Sougato-DasConvention week in San Diego has become much more than a single conference. One of the major events taking place during the week is RESI San Diego 2026, hosted by Life Science Nation on June 22, followed by four virtual partnering days on June 23–24 and June 29–30. This is the best place to secure meetings with early stage investors.

Around RESI and the Convention, investors, founders, pharmas, service providers, and regional delegations host receptions, networking events, investor forums, pitch sessions, private meetings, and educational programs across the city.

For attendees, the week often becomes a full schedule of opportunities that extends well beyond the official conference agenda. A company may attend RESI or Convention during the day and continue conversations at networking receptions and evening events across San Diego.

That is why having a compiled list of convention week events can be so valuable. Life Science Nation has curated a list of convention week events taking place throughout San Diego to help attendees better navigate the week. Covering Sunday, June 21 through Friday, June 26, the list serves as a useful resource for attendees looking to plan their schedules and make the most of their time in San Diego.

The list includes events for a range of audiences and interests, from investor networking and startup showcases to regional receptions, educational panels, business development gatherings, and informal social events. Some events are designed specifically for early-stage companies looking to connect with investors, while others are focused on strategic partnerships, market trends, or geographic regions.

Convention week can also be an important opportunity for companies to make the most of their time in San Diego. Rather than relying on one conference alone, attendees often use the week to build a broader schedule of meetings and introductions.

Whether attendees are focused on fundraising, partnering, business development, or networking, convention week offers a wide range of ways to connect.

View the Compiled List of Convention Week Events

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Innovator’s Pitch Challenge Winner Spotlight: Bram De Moor of You2Yourself 

14 Apr

Following its recognition as a winner of the Innovator’s Pitch Challenge at RESI Europe, You2Yourself is advancing a new approach to early disease detection through longitudinal biomarker monitoring. In this interview, Bram De Moor discusses the science behind URIMON, the company’s commercialization strategy, and how RESI has supported its investor engagement. 

Bram De Moor
Founder & General Manager, You2Yourself
 CaitiCaitlin Dolegowski
Program Director, LSN

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 — including prostate cancer, lung cancer, and cardiovascular disease — 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 — 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 — 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 (€299–499/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 Innovator’s 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 — a highly targeted audience that is difficult to reach through traditional outreach.

The Innovator’s 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 12–18 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 — including advances in NGS, growing demand for preventive health, and regulatory clarity — You2Yourself is well positioned to lead in this space.

Applications are now open for upcoming Innovator’s 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.

Apply to Pitch at RESI San Diego

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The Needle Issue #25

14 Apr
Juan-Carlos-Lopez
Juan Carlos Lopez		 Andy-Marshall
Andy Marshall

The approval of multiple anti-amyloid monoclonal antibodies (mAbs) — aducanumab (Aduhelm; now withdrawn), lecanemab (Leqembi) and donanemab (Kisunla) — over the past five years has opened the era of disease-modifying Alzheimer’s drugs, albeit with only modest benefits in addressing cognitive decline (30% slowing) and associated serious safety risks, such as CNS inflammation and cerebral hemorrhages, which has limited clinical uptake. While many drug development programs target biological processes other than amyloid formation (e.g., tau and tangles, neurotransmitter receptors, neuroinflammation, autophagy, and mitochondrial or metabolic dysfunction), companies continue to optimize anti-amyloid monoclonals, but also look for alternative ways to therapeutically target Aβ.

One alternative therapeutic modality to antibodies is chimeric antigen receptor (CAR) immune cell therapy. In recent weeks, we have been thinking a lot about in vivo chimeric antigen receptor (CAR)-T therapies, which were one of the dealmaking trends in 2025, and we recommend readers check out an excellent summary of trends in the area from the consultancy firm Scitaris (you don’t even have to give them your details to download the report).

CAR-T treatments have established their clinical niche as last-ditch treatments for B-cell malignancies, with some remarkable outcomes for late-stage patients. In some cases, they have been shown to be at least twice as effective as T-cell engager bispecific antibodies in clinical studies. But they remain rather blunt instruments.

Despite advances in the clinical management of cytokine-release syndrome and immune effector cell neurotoxicity syndrome (ICANS), CAR-T treatments continue to be associated with serious risks. And while there have been advances in managing these adverse events, atypical non-ICANS neurotoxicities (NINTs) can also create serious clinical management issues, with risk factors predisposing patients to development still only poorly understood.

That said, over the past year, we have seen an increasing trend for the use of CAR-T treatments outside oncology. They have started to be applied with promising efficacy in various areas of autoimmunity (systemic lupus erythrematosus, lupus nephritis, systemic sclerosis, Sjögren’s syndrome, antisynthetase syndrome, myasthenia gravis and idiopathic inflammatory myopathies) and neuroinflammatory conditions (multiple sclerosis). In this respect, a recent paper in Science caught our attention. In it, Marco Colonna and his colleagues at Washington University in St. Louis harness astrocytes to clear amyloid plaques by promoting their ability to phagocytize Aβ.

To that end, they used in vivo gene therapy to generate astrocytes carrying chimeric antigen receptors (“CAR-As”), a strategy not unlike the one used in cancer immunotherapy. Although both macrophages (CAR-Ms) and conventional CAR-Ts have been tested in preclinical models of Alzheimer’s disease with limited success, this study reports the first attempt to directly engineer astrocytes in the body to generate CAR-As.

In broad terms, the construct used to generate CAR-As consisted of an Aβ-binding domain and the phagocytic signaling protein MEGF10 (multiple epidermal growth factor-like domains protein 10). The team examined a variety of constructs and chose two for in vivo testing. One of them combined a fragment from the Aβ-binding antibody crenezumab and MEGF10, which is primarily expressed in astrocytes. The second construct combined a fragment of aducanumab with the phagocytosis receptor Dectin-1, which is primarily expressed in microglia.

The authors packaged the constructs in an adeno-associated viral (AAV) vector under the control of an astrocyte-specific promoter and injected them intravenously into 5xFAD mice (which carry five familial Alzheimer’s disease (FAD) mutations, driving rapid Aβ plaque formation, synaptic loss, and cognitive decline starting around 2–4 months). Both CAR-As reduced amyloid burden and neuritic dystrophy, and the treatment worked both in the prophylactic and therapeutic settings.

Single-nucleus RNA sequencing and immunostaining showed that the CAR-As adopted the transcriptomic profile of activated astrocytes and readily clustered around amyloid plaques. Microglial cells, in turn, also responded to the treatment by showing a reduction of the disease-associated transcriptomic profile that is often seen after administration of monoclonal anti-Aβ antibodies. This is of interest because this disease profile of microglial cells has been suggested to contribute to the inflammatory reaction sometimes seen after Alzheimer’s immunotherapy.

A caveat of the study is that the authos saw no improvements in cognition following therapy, albeit behavioral results in mouse models have been notoriously poor at predicting outcomes in humans. However, the translational questions don’t stop there.

If in clinical practice the CAR-A approach would require an AAV vector, then immunogenicity of the treatment is going to be an issue. Pre-exposure to AAV is often a problem for gene-therapy programs, where patients are much younger. Given that Alzheimer’s is a disease associated with an elderly population, immunogenicity is likely to be exacerbated. Similarly, the delivery of 1013–1014 viral genomes to elderly patients living with Alzheimer’s—many of whom will already have a brain prone to neuroinflammation—makes the specter of unwanted side effects a major concern. In this respect, finding Alzheimer’s patients whose disease stage and age would be appropriate for a therapy with potentially highly toxic consequences for fragile recipients is also difficult to gauge.

That is not to say that CAR-immune cell therapy may not have a place in CNS disease. It just seems like neurological conditions, such as multiple sclerosis where patients are younger and potentially less fragile, are the place where much of the translational groundwork and clinical management for CAR-A or CAR-T therapies must be worked out before moving into neurodegenerative disease for elderly and cognitively compromised patients.

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