Tag Archives: food

The Needle Issue #9

1 Jul
Juan-Carlos-Lopez
Juan Carlos Lopez		 Andy-Marshall
Andy Marshall

​Drug development efforts targeting the constitutive 26S proteosome have led to the development of several important multiple myeloma (MM) and mantle cell lymphoma treatments, including the first landmark FDA approval of Millennium Pharmaceuticals’ (now Takeda) dipeptide boric acid Velcade (bortezomib) in 2003 and second-generation molecules, such as Amgen/Ono Pharmaceutical’s irreversible inhibitor Kyprolis (carfilzomib) and Takeda’s orally available inhibitor Ninlaro (ixazomib). Second-generation versions of these ‘pan-proteosome’ drugs have longer duration of effect, reduced peripheral neuropathy and increased safety in renally impaired patients, but may cause gastrointestinal and cardiac toxicity. This toxicological profile has shifted attention to developing inhibitors selective for an alternative form of the core 20S proteosome—the immunoproteasome, which processes peptides for presentation to CD8+ T cells in the MHC-I complex and is constitutively expressed only in hematopoietic cells, induced in immune cells stimulated in the presence of IFN-γ, and upregulated in certain cancers like MM.

Currently, Kezar Life Sciences’ is furthest along in development; in April, it completed a phase 2a trial in autoimmune hepatitis of zetomipzomib (KZ-616), a small-molecule that inhibits both the immunoproteasome core particle component beta subunit 8 (PSMB8; LMP7/β5i) and PSMB9 (LMP2/β1i). Merck kGaA (Darmstadt, Germany) is also pushing forward with a phase 1 clinical program of M3258, a small-molecule inhibitor specific for PSMB8 and intended for use in MM (Principia Biopharma’s selective PSMB8 inhibitor was swallowed up by Sanofi in 2020 when the pharma acquired the San Francisco-based biotech’s Bruton’s tyrosine kinase inhibitor program). Elsewhere, Leiden University startup iProtics recently received a €200K grant from the Dutch Biotech Booster to develop selective immunoproteosome inhibitors, while Auburn University spinout Inhiprot (West Lebanon, NH) received SBIR funding to develop a dual PSMB6/PSMB9 inhibitor for MM. Now, a new study reveals immunoproteosome targeting may also have benefits in neuroinflammatory diseases like multiple sclerosis.

The work, published in Cell and led by Catherine Meyer-Schwesinger and Manuel Friese, from University Medical Center Hamburg-Eppendorf, identifies a neuron-intrinsic mechanism of neurodegeneration in multiple sclerosis (MS) driven by the immunoproteasome.

Under healthy conditions, neurons utilize the constitutive proteasome subunit PSMB5 to regulate proteostasis and degrade 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a potent stimulator of glycolysis. This degradation is key because neurons rely more on the pentose phosphate pathway than on glycolysis to produce antioxidants like NADPH and glutathione for protection against oxidative stress.

However, Meyer-Schwesinger, Friese and their colleagues show that, during neuroinflammation, chronic exposure to interferon-γ leads to the induction of the immunoproteasome in neurons, triggering the replacement of constitutive proteosome PSMB5 (β5c) with PSMB8 (β5i). This subunit swap in neurons reduces proteasomal activity, resulting in accumulation of PFKFB3, which in turn enhances glycolysis, diminishes the activity of the pentose phosphate pathway, and impairs redox homeostasis — conditions that sensitize neurons to oxidative injury and ferroptosis.

The team showed that this mechanism was operational in both experimental autoimmune encephalomyelitis (EAE; a mouse model of MS) and brain tissue from MS patients. Moreover, neuron-specific knock-out of Psmb8 or pharmacological inhibition using the small-molecule PSMB8 inhibitor ONX-0914 (originally developed at Onyx Pharmaceuticals/Proteolix) protected neurons in vivo from inflammation-induced damage. Similarly, blocking PFKFB3 with the small-molecule inhibitor PFK-158 or through conditional knockout in neurons reduced disease severity in EAE, prevented neuronal and synaptic loss, and reduced markers of oxidative stress and lipid peroxidation.

It is important to highlight that, unlike cancer or immune cells, neurons do not upregulate PSMB8 in response to a series of MS-related cytokines. So, the neuron-specific effect reported in this study might only become active upon chronic neuroinflammation (i.e. chronic exposure to interferon-γ). Understanding this mechanism might reveal new targets related to the immunoproteosome in the treatment of MS.

This brings us to challenges for translational efforts seeking to develop immunoproteosome inhibitors against MS. Several important neuronal processes, such as synaptic transmission and calcium signaling, are tightly linked to proteasome function; thus, pan-proteosome inhibitors like Velcade could be detrimental to the CNS. The saving grace of approved proteosome inhibitors is that current chemotypes (boronate-based peptides or epoxyketone-based binders) do not cross the blood brain barrier, at least in healthy individuals. Thus, any MS program might need to use intrathecal injection for compounds derived from existing chemical series or engage a medicinal-chemistry effort to design molecules that can breach the BBB and retain potency.

The gambit for immunoproteosome-selective drugs is that they avoid inhibiting constitutive 26S proteosome activity in most tissues (and non-inflammed CNS), which is what makes Velcade and its derivatives so difficult for patients to tolerate; an immunoproteosome inhibitor should therefore have a more favorable safety profile. But so far, immunoproteosome-targeting drugs have had their own share of toxicity problems in the clinic.

Last October, Kezar abandoned its program for zetomipzomib in lupus nephritis after the FDA placed a clinical hold on the trial after 4 patient deaths. The agency placed a second partial hold on the company’s autoimmune hepatitis trial in 24 patients last November due to concerns about steroid control and injection site reactions in 4 patients who were waiting to roll over into the open-label extension arm. Concerns about compromised immune surveillance of acute or latent viral infections due to hobbled antigen processing and presentation would also need to be explored.

In sum, the new work provides strong evidence that the immunoproteosome plays a key role not only in inflammation or infiltration of immune cells, but also in a metabolic switch in neurons which is a key driver of vulnerability in MS. It will be interesting to see whether either targeting immunoproteosome component PSMB8 or taking a completely different tack, blocking PFKFB3, will prove more practical as a neuroprotective strategy in MS.

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The Needle Issue #8

24 Jun
Juan-Carlos-Lopez
Juan Carlos Lopez		 Andy-Marshall
Andy Marshall

Around 1 in 5000 people live with a maternally inherited mitochondrial disease like MELAS, Leber’s Hereditary Optical Neuropathy (LHON) or MIDD, for which there are limited or no treatment options. Gene- and base-editing therapies for mitochondrial DNA (mtDNA) have lagged behind CRISPR–Cas9-based approaches targeting nuclear genes. Whereas there is already a CRISPR–Cas9-based product on the market and >150 different active trials of investigational therapies, the company closest to the clinic with an I-CreI (mitoARCUS) meganuclease targeting a mtDNA point mutation in MELAS/mitochondrial myopathy (Precision Biosciences) announced last month that it was pausing development for commercial reasons.

Despite this disparity, there is reason for optimism as a flurry of different types of optimized cytidine and adenine base editors for mtDNA are now available, with base conversion efficiencies of 50% now achievable, and some newer formats reaching efficiencies as high as 82%.

The development of mtDNA editors is not without challenges. First, editors must dispense with the targeting guide RNA, as mitochondria possess a double membrane that lacks any RNA transport system, effectively thwarting CRISPR-based gene or base editors (instead, a mitochondrial targeting sequence is used to ferry-in editor proteins). Second, unlike nuclear DNA with two copies of a gene, every human cell contains thousands of mitochondria — oocytes contain a whopping 193,000 mitochondria on average — and each organelle contains an average 10 mitochondrial genomes. Those ~10,000 genomes per cell may not all have the same sequence, with mutations existing in a state known as heteroplasmy, in which both mutant and wild-type genomes co-exist in the same organelle. Disease only occurs when the percentage of mutant mtDNA exceeds a particular threshold, typically between 70% and 95%.

Heteroplasmic mitochondrial diseases, like MELAS and MIDD, could be treated using I-Crel/FokI meganucleases or restriction enzymes linked to either transcription activator-like effector (TALE) domains or zinc fingers (which introduce double-strand DNA breaks into target sequences, leading to elimination of mutant mtDNA and repopulation of wild-type mtDNA); other conditions like LHON are predominantly mutant homoplasmic, which means they can only be treated using base editors or supplemental gene therapy.

One key concern with base-editing technology has been its propensity for off-target and bystander changes. This has led to various strategies to increase specificity, such as engineering the deaminases to narrow the editing window or use of nuclear exclusion sequences to stop nuclear sequence editing. Now, two papers in Nature Biotechnology represent important advances that could speed up translational studies of mitochondrial diseases.

Liang Chen, Dali Li and their colleagues of ShanghaiTech University, China report the engineering of highly efficient mitochondrial adenine base editors (eTd-mtABEs) by introducing mutations into the TALE TadA-8e deaminase for greater activity and specificity. These editors achieved up to 87% editing efficiency in human cells and over 50% in vivo, with reduced off-target effects compared to earlier tools.

In the first study, the researchers used eTd-mtABEs to introduce mutations in the human ND6 gene, encoding a subunit of the oxidative phosphorylation (OXPHOS) system linked to LHON and Leigh syndrome. They found reduced levels of ATP and more reactive oxygen species in the edited cells compared with controls, consistent with disease phenotypes. Next, the team used this adenine TALE base editor to introduce two pathogenic T-to-C mutations in the mitochondrial TRNS1 gene of rat zygotes, a gene linked to childhood-onset sensorineural hearing loss. The resulting offspring showed sensorineural hearing loss, which was transmitted to the F1 generation, providing proof of concept that eTd-mtABEs can be used to create animal models of disease.

In the companion paper, Chen, Li and their colleagues used the adenine TALE base editor to model Leigh disease in rats using a similar strategy. The resulting rats showed reduced motor coordination and muscle strength, defects that were obtained with editing efficiencies of only 54% on average. To test if the abnormalities could be reversed, the authors then used a cytosine TALE base editor in zygotes from the mutant rats. On average, the editing efficiency was only 53%, but this was enough to rescue the disease phenotypes.

This is the first report of direct correction of mtDNA mutations via a TALE base editor in an animal model. The next step will be to show feasibility in a model after disease onset (only the UK and Australia allow maternal spindle transfer therapy for mitochondrial diseases; no country has permitted mitochondrial base editing in human zygotes).

Achieving effective therapeutic mitochondrial base editing in affected target tissues will thus require efficient AAV delivery. For LHON, an already approved FDA AAV-2 product transduces the optic nerve and retinal ganglion cells, providing a translational path; ​GenSight Biologics also recently published 5-year outcome data for its AAV-2 therapy Lumevoq (lenadogene nolparvec) in LHON. But AAV delivery in other mitochondrial conditions will not be as simple: MELAS patients, for example, require efficient transduction of the CNS, kidney, skeletal muscle and cardiac muscle; MIDD patients need AAV delivery to the pancreas, inner ear, retina and kidney. Although a commercial AAV vector (AAVrh74) is available for muscle (Sarepta’s Elvidys), vectors that reach many of these other tissues have yet to be commercialized and may require next-generation AAV capsids and/or refinement of machine-guided design of cell type-specific synthetic promoters to reach target organs.

It is encouraging that the roughly 50% base conversion rate achieved in these new studies exceeded the heteroplasmy threshold required for disease manifestation and therapeutic rescue. At the same time, despite this remarkable success, concerns remain about off-target effects — both in mitochondrial and nuclear genomes — and narrow therapeutic windows. And with base editing approaches so far behind conventional gene therapies like Lumevoq in development, compelling commercial and clinical advantages benchmarked against best-in-class gene therapy will be needed to convince investors to back these approaches.

One parting thought: the past year has seen a noticeable uptick in publications on mitochondrial base editing technology from labs outside of the US. TALEN specialist Cellectis, headquartered in Paris, France, acquired 19% of equity in the mitochondrial base editing company Primera Therapeutics in 2022, ostensibly for its rapid TALE assembly platform (FusX System), which streamlines TALE repeat construction. In South Korea, Jin-Soo Kim at the Korea Advanced Institute of Science and Technology (KAIST) recently co-founded startup Edgene with Myriad Partners to develop mitochondrial base editors based on his seminal work on TALE-linked deaminases (TALEDs) enabling A to G conversion, which he has continued to optimize. According to Biocentury, 8 out of 13 base editing studies published in 27 translational journals over the past year came from labs in China. Wensheng Wei’s group at Peking University, a founder of Edigene in Beijing, continues to work on mitobase editors, with two recent patents on strand-selective mitochondrial editing. And Jia Chen of ShanghaiTech University, China, and his collaborators Li Yang and Bei Yang, are scientific advisors to Correctseq in Shanghai, which is developing transformer base editors for ex vivo and in vivo applications. It seems that mitochondrial base editing may be another area where US biotech may soon be finding itself chasing the dragon. David Liu and Beam Therapeutics may have something to say about that.

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The Needle Issue #7

10 Jun
Juan-Carlos-Lopez
Juan Carlos Lopez		 Andy-Marshall
Andy Marshall

Ex vivo HSC lentiviral gene therapies have been on the market for nearly a decade, with six products approved and at least 55 now in clinical testing for rare inherited diseases, HIV infection or cancer. And yet, their commercial success remains in question. Bluebird Bio—which was valued at $10 billion only a few years ago and successfully shepherded to market Zynteglo against transfusion-dependent β-thalassemia, Skysona for early cerebral adrenoleukodystrophy, and Lyfgenia for sickle-cell disease (SCD)—was sold earlier this year to private-equity firms Carlyle and SK Capital for a measly $29 million. Last November, the company had treated only 57 patients (35 for Zynteglo; 17 for Lyfgenia and 5 for Skysona), with just 28 of 70 medical centers across the US ready to treat patients due to delays in accreditation and training of personnel. In Europe, Orchard Therapeutics halted marketing and production of a treatment for severe combined immunodeficiency caused by adenosine deaminase mutations (Strimvelis) after six years, forcing Fondazione Telethon to take over production. Even market uptake of Vertex’s much-heralded CRISPR/Cas9 BCL11a SCD therapy Casgevy has been sluggish.

These subpar commercial launches relate to the complexity of ex vivo lentiviral gene therapy: patient identification and qualification is lengthy; HSC mobilization and sourcing efficiencies vary due to patient heterogeneity; and manufacture and distribution processes remain lengthy and convoluted (sometimes requiring repetition if a poor quality product batch is generated). From first evaluation, patients are required to make several hospital visits over a period (of up to a year) and must undergo punishing conditioning regimes with lymphodepletive bisulfan before infusion, which itself carries infertility and cancer risks. All of these challenges have added impetus to the search for alternative and more efficient approaches for carrying out HSC gene therapy.

​A group led by Alessio Cantore and Luigi Naldini, from the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy, report in Nature that it may be possible to obviate these challenges by delivering recombinant lentiviral vectors in vivo soon after birth, when HSCs continue to circulate in the bloodstream in large numbers and are beginning their transition from the liver (where they are located in the fetus) to bone marrow (where they remain through adulthood).

Cantore, Naldini and their colleagues started by measuring the number of circulating HSCs in neonatal, 1-, 2- and 8-week-old mice, looking at the peripheral blood, spleen, liver and bone marrow. They found that HSCs were present in the circulation right after birth and that their number immediately declined. These cells could be transduced with lentiviruses, successfully engrafted, and persisted in the mice for several months.

To show that these HSCs could be harnessed to treat genetic disorders, the team tried to correct three mouse models of disease — adenosine deaminase deficiency, autosomal recessive osteopetrosis and Fanconi anemia. Although the therapeutic effect of the cells varied depending on the disease, the results provided compelling evidence for the potential for in vivo gene transfer to HSCs.

The authors reported that human neonates also have circulating HSCs in high numbers. And although the therapeutic window in the mouse only existed during the neonatal period, it was possible to lengthen it by mobilizing the HSCs from their niche in two-week-old animals using protocols in clinical use (granulocyte-colony stimulating factor/CXCR4 antagonist Plerixafor) These observations raise the possibility of therapeutically targeting HSCs in newborns, potentially opening the gates to treatment of a variety of inherited conditions.

Compared with the headaches of ex vivo manipulation, the authors’ concept of simply injecting a lentiviral gene therapy into a newborn to bring about a genetic cure is certainly alluring. But reducing this to clinical practice will require optimization of many different factors. How to account for the heterogeneity and fragility of patient HSCs in a particular disease? How to measure the cellular activation/metabolic state of HSCs in newborns and assess the affect on amenability to lentiviral transduction in the hostile milieu of blood? What effect would shear stress in circulation have on lentiviral transduction efficiencies in situ? What would be the selective engraftment advantage provided to HSCs after engraftment of a particular gene? And what would be the potential safety implications of off-target transduction events in cells other than HSCs, given instances of dysplastic syndromes have been reported with ex vivo lentivectors?

Current ex vivo lentiviral gene therapy like Lyfgenia and Zynteglo infuse between 3–5×106 gene-modified CD34+ HSCs/kg in a patient. The challenge for in vivo lentiviral gene therapy will be to achieve transduction efficiencies that transduce as many cells and obtain similar engraftment rates in the rapidly turning over HSC population. Beyond these issues, there are additional practical challenges: can genetic testing of an infant happen fast enough to take advantage of the short therapeutic window for which an in vivo lentiviral HSC therapy could work?

Clearly, the new work raises many intriguing questions for the lentiviral gene therapy space. And for newborns with genetic diseases, such as severe immunodeficiencies or Fanconi anemia, in vivo HSC gene therapy may open up new treatment options.

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Engineering Breakthroughs: How Tecan Partners with MedTech Innovators to Scale Smarter 

3 Jun

At RESI Boston June, Tecan joins as a sponsor, and a strategic development partner for early-stage MedTech and life science companies. In this interview, Jed Palmer, Director of R&D and Engineering, shares how Tecan supports innovators from prototype to scalable product, what technologies they’re excited to partner on, and what startups can do to stand out in the eyes of a seasoned engineering team.

Jed Palmer CaitiCaitlin Dolegowski

Caitlin Dolegowski (CD): Can you briefly introduce Tecan and your role within the company, particularly as it relates to partnering and innovation?

Jed Palmer (JP): Tecan partners with companies across life sciences, diagnostics, and MedTech as an integrated, global development and manufacturing organization. Within Tecan, our Technology Development group works closely with MedTech innovators to bring breakthrough technologies from concept to working prototype in months, not years. From there, Tecan supports the transition to manufacturable, scalable solutions through our global network and operations

In my role as Director of R&D, I lead cross-functional teams of engineers and scientists who specialize in early-stage system design, particularly for electronics-based, energy-delivering and high-precision medical devices. We work closely with startups and emerging technology companies to overcome integration, prototyping, and scalability challenges, acting as a true extension of their R&D team.

CD: What motivated Tecan to sponsor and attend RESI Boston this year? What makes this conference valuable to your team?

JP: RESI Boston is one of the premier conferences that brings together a critical mass of early-stage life sciences and MedTech innovators who are actively looking for partnership, not just exposure. For us, it’s a unique opportunity to connect with founders and technical leaders who are right at that moment where concept validation meets real-world execution.

We sponsored RESI because we believe our customers’ technologies have the power to shape the future of healthcare and drive meaningful impact. As engineers, we want to be at the center of that innovation, working side by side with our partners. Our goal is to be a true strategic collaborator, not just a service provider, offering deep technical expertise and scalable platforms that help turn promising ideas into transformative, market-ready products.

CD: What types of early-stage companies or technologies are you most interested in connecting with at RESI? Are there particular therapeutic areas or platforms that align with Tecan’s strategic goals?

JP: We’re especially interested in early-stage companies developing energy-based therapies, electrophysiology tools, neuromodulation platforms, and next-gen surgical systems, particularly those integrating complex electronics or control systems. Therapeutic areas that align closely with our strategy include:

  • Cardiac and electrophysiology devices
  • Minimally invasive surgical technologies
  • Implantable and wearable therapeutics
  • Neurotech platforms

We partner with teams solving tough engineering problems in power delivery, system integration, miniaturization, etc. Our goal is to accelerate their journey to functional prototype and scale.

CD: How does Tecan typically engage with startups? Are you looking to collaborate through investment, strategic partnerships, technology licensing, or another model?

JP: Our approach is very hands-on and partnership-driven. We focus on collaborative technology development, acting as an extension of our partners’ R&D team—bringing a multidisciplinary group of engineers, physicists, and system architects to accelerate progress.

We understand that no two companies or technologies are the same. Whether it’s a short-term technical challenge or a long-term product roadmap, we work with our partners to define a structure that aligns with their goals, resources, and timelines. Our focus is on building the kind of partnership that delivers meaningful value.

CD: What advice would you give to early-stage companies looking to capture the interest of a company like Tecan at a partnering conference?

JP: The most compelling startups are the ones who are clear on what problem they’re solving—and have a grounded view of what they need help with. You don’t need to have everything figured out. What resonates with us is clarity around the application, an understanding of technical gaps, and openness to collaborative development.

Also, don’t be afraid to bring your early challenges forward. We’re not just here for polished decks—we’re here for the engineering friction points, the integration problems, and the roadblocks that need real solutions.

CD: Are there any common challenges you see when evaluating potential partners in the life science ecosystem, and how can companies better prepare to overcome them?

JP: In the early stages of technology development, it’s very common to not recognize the assumptions that were made in designing a treatment. We like to see teams that are open to having those assumptions challenged in order to progress the technology.

Another common challenge is underestimating the time and complexity required to move from proof-of-concept to a robust, testable prototype. Teams often get stuck when transitioning from feasibility to development because the architecture wasn’t built with flexibility or scale in mind.

Companies can better prepare by thinking about system-level design earlier in their process. Bringing in a development partner with deep hardware/software integration experience can help avoid costly rework, especially for energy-delivering or electronics-driven devices. Early conversations around testability, firmware strategy, and control platforms can save months.

CD: Looking ahead, what trends or innovations in the life sciences space are you particularly excited about, and how do they align with Tecan’s long-term vision?

JP: We’re particularly excited by the convergence of energy delivery technologies, real-time sensing, and closed-loop control, especially in areas like Neurostim technologies and electroceuticals. These are areas where modular, scalable architectures can unlock faster development. We’re also watching the push for personalized and distributed care, which demands smaller, smarter, and more adaptable devices.

Our long-term vision is to be the go-to partner for teams looking to innovate faster and scale smarter. RESI is one of the places where that journey starts.

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Redefining Emergency Care: An Interview with Opportunity Health 

6 May

Third-place winner at the RESI Europe Innovator’s Pitch Challenge discusses their breakthrough anti-choking device and plans for market launch. 

Interview with Iñigo Almazán Tife, Industrial Design Engineer of Opportunity Health by Caitlin Dolegowski, Marketing Manager, LSN

Iñigo Almazán Tife CaitiCaitlin Dolegowski

We sat down with Iñigo Almazán Tife, from Opportunity Health to learn more about the inspiration behind their life-saving innovation, their experience at RESI Europe, and what lies ahead for the company. Opportunity Health recently took third place in the Innovator’s Pitch Challenge at RESI Europe, and their technology is generating attention for good reason. 

Caitlin Dolegowski (CD): Tell us about the origin of Opportunity Health and the innovation behind your solution. 

Iñigo Almazán Tife (IT): Opportunity Health began with a deeply personal event. Our CEO, Germán, was inspired to create this company after a frightening incident involving his brother, Txema. Txema began choking during a family dinner. Thankfully, their father had some knowledge of how to perform a life-saving intervention and managed to save him. But the family recognized it could have ended very differently—had Theo been alone, the outcome might have been fatal. That moment sparked the idea behind our solution. 

The result is Yarnasa, the first automatic, self-applicable anti-choking device. It’s designed for emergency situations and intended to be simple and intuitive—something that can be used in the moment, even by the person who is choking. 

CD: Can the device be used on both adults and children? 

IT: At this stage, our focus is on adults and individuals over the age of 12. This decision is driven by data: around 90% of fatal choking cases occur in individuals over the age of 65. Once we validate the product for adults, our plan is to begin trials to adapt and validate its use for children as well. 

CD: What stage of development and fundraising is Opportunity Health in now? 

IT: We’re currently patent pending and preparing for CE marking in the European market. Our aim is to launch commercially in Europe by mid-2027. The regulatory process for medical devices in Europe typically takes about two years, so we’re laying the groundwork now. 

In parallel, we’re looking ahead to securing FDA clearance for the U.S. market. However, we currently need additional resources to begin that process. One of our near-term goals is to secure funding to pursue FDA certification in parallel with our European regulatory strategy. 

CD: How does your device compare to existing solutions? 

IT: There are other anti-choking devices on the market, but ours is fundamentally different. Most existing options require prior knowledge or physical effort from another person. That becomes problematic if, for example, the person assisting is also elderly or not physically capable. 

Yarnasa is fully self-applicable and automatic. There’s no need for training or strength—just activate it, place it, and press a button. We’re offering a premium, highly innovative solution that redefines the category of anti-choking devices. 

CD: You took third place in the Innovator’s Pitch Challenge at RESI Europe. What was your experience like? 

IT: RESI Europe exceeded our expectations. It was incredibly well organized and offered a strong platform for networking. We met potential investors and collaborators who provided feedback not only on the product but also on company strategy and market approaches. 

The only improvement we’d suggest is better alignment between registered investors and actual attendance. Some investors were only available virtually, which made coordination a bit challenging. But overall, it was a very positive experience. 

CD: How was your experience with the Innovator’s Pitch Challenge itself? 

IT: The Pitch Challenge gave us valuable exposure and feedback. Beyond the pitching session, being part of the exhibition hall allowed us to interact with a wide range of stakeholders. We had insightful conversations about go-to-market strategies across Europe and the U.S., which gave us a clearer roadmap for commercialization. We walked away with actionable insights and new connections. 

CD: Did RESI Europe help you take any steps forward in your fundraising efforts? 

IT: Yes, absolutely. We made new investor connections and followed up by sharing our deck. We’re now in active conversations. Fundraising is a long process, of course, but RESI helped us move things forward. 

CD: What are your goals for the next year or two? 

IT: In the coming months, we’re focused on finalizing our prototype for industrial production, targeting September of this year. After that, we plan to launch an investment round by the end of 2025 or early 2026. The goal of that round is to fund the company through the final development phase and launch the product in market. 

CD: What advice would you give other companies preparing to pitch at RESI? 

IT: I wouldn’t call myself an expert in pitching, but from our experience, I’d say preparation is key. Be clear about the main message you want to convey. And most of all, enjoy the event—be open to conversation. You never know who you’ll meet, and those connections could play a vital role in your company’s journey. 

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Meet Meki Durakovic: The Hospitality Force Behind Boston’s Culinary Hotspots

22 Apr

Interview with Meki Durakovic, a Visionary Restaurant Owner by Caitlin Dolegowski, Marketing Manager, LSN

Meki Durakovic CaitiCaitlin Dolegowski

For life science professionals attending RESI and Bio in June, Boston offers more than innovation—it offers unforgettable hospitality. One of the city’s driving forces behind that experience is Meki Durakovic, a restaurateur whose journey from Europe to Boston has transformed the local dining scene.

Meki got his start running his family’s restaurant at 19 and quickly became known for hosting community events and building customer loyalty. After gaining global experience in Germany, he moved to Boston in 1996, working his way through every level of the hospitality business—from the kitchen to management—ultimately joining the influential Lyons Group.

Today, Meki is the co-owner of some of Boston’s most dynamic venues: Fin Point Oyster Bar & Grille, Tradesman Coffee, Lily’s, Amber Road, Urban Wild, One Beacon, and more. His venues mix warm hospitality, locally sourced menus, and inviting atmospheres perfect for both after-hours business gatherings and casual networking.

As the life sciences world converges on Boston this June, Meki’s restaurants offer more than just meals—they offer a taste of the city’s spirit. Make sure to experience his take on Boston hospitality while you’re in town.

Caitlin Dolegowski (CD): Could you tell us about your Restaurant Group and the several standout restaurants in Boston? Can you describe each one and what makes it unique?

 Meki Durakovic (MD):

  • Tradesman – Best Coffee Shop in Boston with unique pastries & specialty croissants, fresh sandwiches and more. We have Tradesman locations on Broad Street and Federal Street in the financial district as well as in Charlestown. (50 Hood Park Dr. Charlestown, MA )
  • Amber Road – Our newest venue which boasts an open-kitchen, open air concept and patio and serves refined global-inspired New England cuisine, craft cocktails, and an extensive wine list. We recommend this space for elevated full private buyouts for events up to 180 guests. (100 Federal St, Boston, MA)
  • Fin Point – The first restaurant opened by our group that has become the place to be in Boston’s downtown Financial District. Here we host everything from corporate lunches and impressive cocktail receptions to weddings, full corporate buyouts for 200 guests and more. The sophisticated dining space features a raw bar and high-end seafood dishes with global influences. (89 Broad St, Boston, MA)
  • Urban Wild – Boston’s newest entertainment destination features high-tech bowling like you’ve never seen, indoor and outdoor patios with games, and a giant beer garden covered in custom artwork for a true experience. The venue holds up to 600 guests and is located in Charlestown’s quickly growing Hood Park Neighborhood. (100 Hood Park Dr, Boston, MA)

CD: For visitors coming to Boston for RESI and the Bio convention in June, which of your restaurants would you recommend for a great dining experience?

MD: All of the above!

CD: Could you tell me what guests should know about making reservations at your restaurants? Do you recommend booking in advance, and how far out should they plan?

MD: Reservations can be made online on Open Table or by calling directly. Reservations for bowling at Urban Wild can be made 7 days in advance on our website. For events, email our Director of Events, Katie Lofstrom, at events@mnmrestaurantgroup.com

CD: For those looking to take a meeting over a meal, which of your restaurants provides the best setting for a business lunch or dinner?

MD: Fin Point has a fully private dining room perfect for those more private, important meetings and occasions. The room seats up to 20.

CD: What would you advise for those seeking an event where they book a space for a networking event, or want to book the whole bar or restaurant? Please describe your menus, cuisines, and creative dishes. What are some must-try items for first-time guests?

MD: Any of our venues are perfect for hosting full private buyouts. We make the planning process easy!

CD: If RESI attendees seek a spot to gather with colleagues after the conference, do any of your restaurants have bar seating, lounge areas, or late-night options?

MD: All of our venues have bar & lounges, perfect for late-night or mingling after work or after dinner!

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MOWOOT Wins RESI EUROPE 2025 Innovator’s Pitch Challenge (IPC)

22 Apr

Interview with Dr. Markus Wilhelms, CEO & Co-founder by Greg Mannix, VP, EMEA Business Development, LSN

Dr. Markus Wilhelms Greg Mannix

Following their first-place win at the RESI Europe 2025 Innovator’s Pitch Challenge, Dr. Markus Wilhelms, CEO and Co-founder of MOWOOT, discusses their technology, fundraising plans, and what lies ahead for the company.

Greg Mannix (GM): What inspired the development of MOWOOT’s technology, and what unmet need are you addressing?

Markus Wilhelms (MW): Bowel dysfunctions and intestinal transit disorders like chronic constipation affect up to a quarter of the population, often caused by faulty colonic movement patterns. Current treatments are pharmaceutical or invasive and focus on managing symptoms, not addressing the root cause. Our ‘Intermittent Colonic Exoperistalsis’ technology, developed in collaboration with one of Europe’s leading neurorehabilitation hospitals, provides a non-invasive, wearable solution. The MOWOOT device acts as a pacemaker for the large intestine, mobilizing the feces and stimulating proper colonic movement in just 20 minutes a day. This easy-to-use and non-threatening approach offers high clinical response rates and strong patient adherence, without the side effects of conventional treatments.

GM: What stage of fundraising are you currently in, and what types of investors are you hoping to connect with?

MW: Our device is already available in several EU markets, with private & public case-by-case reimbursement secured. We aim for broad public healthcare reimbursement in the UK and Germany by 2025 and are currently raising €10M to support our EU expansion and US market entry in 2026. We are open to discussions with all types of investors, including business angels, family offices, VCs, and strategic corporate investors, as long as we align on deal terms, ticket size and vision.

GM: How has RESI Europe contributed to your fundraising or networking efforts?

MW: RESI Europe provided valuable networking opportunities with investors globally. We had productive meetings during the event as well as on the online platform and are now following up to deepen these conversations.

GM: What was the most valuable aspect of participating in the Innovator’s Pitch Challenge?

MW: Winning the IPC validated our investment opportunity and increased our visibility. It helped us reach investors who might have missed us due to packed schedules, creating additional endorsement and exposure.

GM: What kind of feedback did you receive from the judges or investors during the event?

MW: The feedback on our presentation was very positive, with the jury particularly highlighting the clarity of everything regarding technology, regulatory, and clinical evidence. Most of the questions focused on use of funds, market access strategy and details of reimbursement requirements across different regions, which we were able to address during the Q&A. Given the time constraints of the 6-minute pitch, the Q&A provided a valuable opportunity to fill in any gaps.

GM: How does your team plan to build on the momentum from RESI Europe?

MW: We are actively following up with all new contacts and continuing to receive investor inquiries, thanks to our IPC win. Our data room is prepared, and we expect to move into due diligence with several candidates soon.

GM: What’s next for MOWOOT in the coming 6–12 months?

MW: Over the next 6-12 months, our goal is to secure broad public healthcare reimbursement in the UK and Germany, and we anticipate that scaling in these markets will require robust marketing support. Additionally, we are preparing for a new clinical trial designed to meet the specific reimbursement requirements in France and the US, as confirmed in discussions with local authorities. It’s an exciting period ahead, marking the beginning of our scale-up phase!

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