By Max Braht, Director of Business Development, LSN
Showcase your brand, services, and expertise to a global life science audience
Life Science Nation (LSN) is introducing a new opportunity at RESI JPM 2026, the Company Presentation Track, designed for service providers, established companies, and later-stage ventures seeking to elevate their brand visibility and connect with decision-makers across the global life science ecosystem.
Taking place January 12-13, 2026, at the Marriott Marquis in San Francisco, RESI JPM will also feature three days of virtual partnering on January 14, 19–20. RESI JPM will bring together hundreds of early-stage life science and healthcare companies and over 500 global investors for two full days of partnering, investor panels, and networking.
The new Company Presentation Track offers organizations a unique platform to deliver a 15-minute presentation highlighting their business, market positioning, and value proposition. Unlike the Innovator’s Pitch Challenge, which focuses on fundraising and investor feedback for early-stage startups, these company presentations are designed for firms looking to expand their visibility, attract new clients, and strengthen their strategic partnerships.
Participants in this track will have the opportunity to:
Present their company, products, and services to an engaged global audience.
Build brand recognition among investors, partners, and industry peers.
Demonstrate thought leadership and industry expertise in a highly visible format.
This new feature adds to RESI’s robust mix of investor panels, workshops, partnering meetings, and exhibition opportunities, making it a comprehensive platform for business development and partnership-building across the life science sector.
Make your mark at RESI JPM. Share your story, elevate your brand, and connect with investors, innovators, and service providers driving the future of healthcare innovation.
To apply, select Company Presentation during your RESI JPM registration or contact the RESI team at RESI@lifesciencenation.com for more information.
This year’s Nobel Prize for Physiology or Medicine was awarded to Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi for the discovery of regulatory T cells (Tregs)— white blood cells whose role it is to suppress overactivation of our immune system. The prize was unusual in that Brunkow made her discoveries while leading an industry R&D team at Darwin Molecular (now defunct). Ramsdell and Sakaguchi are also co-founders of two prominent biotech companies developing Treg therapies: Ramsdell’s Sonoma Biotherapeutics is developing autologous Treg therapies against arthritis and hidradenitis suppurativa, together with a LFA3-IgG1 fusion molecule for depleting CD2+ effector T cells; and Sakaguchi’s Coya Therapeutics is developing a low-dose interleukin 2 (IL-2)/CTLA-IgG1 fusion combination for amyotrophic lateral sclerosis and other neurodegenerative disorders; the Nobel prize likely helped boost Coya’s announcement in October to raise $20 million in follow-on funding on the public markets.
Tregs suppress the ability of antigen-presenting cells (APCs) to present antigen to and co-stimulate effector T cells (Teff). In the lymph nodes, the TCR of a Treg cell binds the antigen–major histocompatibility complex (MHC) displayed on the APC, while Treg CTLA4 binds CD80 and CD86 on the APC, blocking Teff access to the same antigen. Tregs also release regulatory cytokines, such as IL-10 and transforming growth factor β (TGFβ), to suppress inflammation. In addition, Tregs express the high-affinity IL-2 receptor CD25, which outcompetes the IL-2 receptor of Teffs. Tregs also express the CD39 and CD73, ectonucleases that convert ATP to adenosine, another anti-inflammatory molecule. Last, Tregs establish a long-lasting tolerogenic environment by turning Teffs into Tregs. Source: Nature Reviews Drug Discovery.
Tregs have long attracted the attention of drug developers interested in autoimmune conditions, diseases where the immune system is overactive. But progress in this field has been slow, and the first clinical results for T-reg cell therapies are only now beginning to emerge in liver transplantation and kidney transplantation. (Low-dose IL-2 treatments that promote Tregs have also begun to show promise in lupus and systemic sclerosis patients.)
The overarching idea behind Treg cell therapy has been to isolate these cells from a patient, introduce/upregulate expression of the FOXP3 transcription factor that marks them from other T cells, and expand them before giving them back to the patient.
Tregs are commonly isolated based on their expression of CD4+ CD25high CD127− and CD45RA+. CD4+ T cells can also be engineered to express FOXP3, the master regulator of Treg development. Tregs can be expanded ex vivo using a polyclonal T cell stimulus like low-dose IL2, small molecules like rapamycin, or (preferably) exposing them to APCs carrying disease-relevant antigens, aiming to enrich the Treg population for a specific antigen. Tregs can also be engineered by expressing a TCR or CAR. The resulting cells are then administered to patients, often together with other immunosuppressive agents. Gene editing has also been proposed as a mechanism to enhance the function and stability of Tregs. Source: Nature Reviews Drug Discovery.
Early attempts to develop this autologous therapy failed in part because Tregs are less numerous in the peripheral blood than effector CD4/CD8 T cells, difficult to isolate and problematic to expand. Moreover, the isolated Tregs are polyclonal, targeting multiple antigens. Approaches that expanded this unmodified polyclonal population of cells and put them back into patients resulted in a ‘diluted’, clinically insignificant, therapeutic effect.
To address this problem, companies are now turning to leverage advances in the chimeric antigen receptor (CAR)-T cell therapy field. A whole slew of Treg cell therapies is being engineered with CARs or T-cell receptors (TCRs), allowing targeting to specific antigens in specific organs.
As we mentioned above, the most advanced of these are in the organ-transplantation field, where chronic immunosuppression renders patients susceptible to infections that can be lethal. Sangamo Therapeutics’ TX200 and Quell Therapeutics’ QEL-001 are CAR-Treg therapies for renal- and liver-transplant rejection, respectively. These assets, which are in phase 1/2, both bind to human leukocyte antigen HLA-A2, which is exclusively expressed on the transplanted donor organ, ensuring that the Tregs travel exclusively to the place where they are needed. Elsewhere, Sonoma is also developing an autologous CAR-Treg therapy, SBT-77-7101, that targets citrullinated proteins abundant in rheumatoid arthritis (for which Sonoma recently announced positive interim phase 1 data) and the skin condition hidradenitis suppurativa.
A second focus for companies has been on TCR-engineered Tregs. The great theoretical advantages of TCRs over CARs are that 1) they have high sensitivity at low antigen density, 2) they focus exclusively on antigen-presenting cells which then reeducate/suppress effector T cells; 3) they don’t bind soluble antigen and 4) most autoimmune diseases are driven by intracellular proteins presented as processed peptides in the context of HLA. As yet, however, only a few companies are pursuing the approach. One example is GentiBio, which is developing GNTI-122 for type 1 diabetes. This Treg product expresses a TCR targeting a fragment (IGRP 305–324) of the pancreatic islet-specific antigen glucose-6-phosphatase catalytic subunit-related protein (IGRP). Another pioneer in this area, Abata Therapeutics, had also been developing a TCR-engineered Treg therapy (targeting myelin peptide/HLA-DRB1*15:01 for multiple sclerosis); however, the frosty financing environment in the first half of 2025 meant it ran out of cash and Abata closed its doors in August.
One challenge that all Treg cell therapies face is the plasticity of these cells and their tendency to shape shift into effector T cells, a phenotypic change that, in the therapeutic setting, could lower efficacy or even exacerbate pathology. One approach to address this problem has been to modify the cells by overexpressing the transcription factor FOXP3, the master regulator of Treg development. For example, as methylation of the FOXP3 promoter under inflammatory conditions can turn Tregs Into effector T cells, Quell’s Tregs are engineered with a methylation-resistant FOXP3 that compels the cells to remain in their suppressor phenotype. And to bring us back to where we started, Nobel laureate Sakaguchi turns out to be a serial entrepreneur, founding another company, Regcell, that recently relocated from Japan to the US on the back of a $45.8 million financing back in March. The company is using small-molecule CDK8/19 inhibitors that act as epigenetic modulators to lock in FOXP3+ Tregs that show a stable suppressive phenotype in vivo.
But Treg cell therapies still face stiff competition. Ironically, perhaps, from their antithesis: the effector CAR-T cell. Pioneering work by Georg Schett’s group at Friedrich Alexander University Erlangen-Nuremberg has galvanized numerous efforts to develop CAR-T depleters of pathogenic B-cell or plasma-cell subsets in autoimmune conditions. Evidence is growing for the clinical efficacy of this approach in diseases such as lupus or myasthenia gravis.
But the holy grail would be to dispense with cell therapy altogether and promote Treg activity in situ, without the need for purification and modification/expansion outside the body. By focusing on injectable biologics, many companies can bring products to market that are easily accommodated into current clinical practice, dispensing with the need for leukopheresis (an approach alien to most rheumatologists) and the complex logistics of ex vivo cell therapy.
The Treg field can rightly celebrate its Nobel recognition and the progress made towards bringing this cell type to patients. Although it will likely be several years before we gain a full picture of how Treg biology can be leveraged to fight autoimmune disease, the field eagerly awaits the readout from early efficacy trials of cell therapies and potentially an FDA-approved product for the biologics in later development.
By Max Braht, Director of Business Development, LSN
JPM week is coming fast, and the best opportunities go to those who plan early. If you still haven’t secured a venue or partnering space, Life Science Nation (LSN) has your solution. As the host of RESI JPM, LSN is opening Sunday partnering at the Marriott Marquis, giving attendees an extra day to meet face-to-face with fellow RESI participants or connect informally outside the partnering system before the main event begins.
Sunday partnering provides a head start on the biggest week in healthcare investment, whether you’re scheduling investor meetings, gathering your team, or hosting your own private event. The Marriott Marquis is at the center of the JPM ecosystem, making it the perfect base for receptions, showcases, and partnering tables throughout the week.
If you represent a membership organization, this is your chance to give your members valuable exposure and a convenient home base in San Francisco—without the steep prices other hotels are charging for table rentals. And for product or service providers, sponsoring or exhibiting at RESI remains the most direct and cost-effective way to meet early-stage innovators. Unlike other partnering events, RESI’s community welcomes vendor meetings, and our partnering stats show that clearly.
Life Science Nation is here to help you make the most of the biggest week of the year. Whether you’re planning a private reception, setting up a partnering table, or joining RESI as an exhibitor, our team can help you build visibility, secure meetings, and connect with the early-stage life science community that gathers at JPM each January.
Register RESI JPM by Friday, October 24 to save $600 on early bird rates!
On September 24, uniQure reported 36-months positive topline data from the phase1/2 study of their candidate AMT-130 for the treatment of Huntington’s disease. AMT-130 consists of viral vector AAV5 and a synthetic miRNA that targets exon 1 of the huntingtin gene. The results showed that AMT-130, directly injected into the striatum at a dose of 6 x 10^13 genome copies per subject, slowed disease progression at 36 months, as measured by the composite Unified Huntington’s Disease Rating Scale and by Total Functional Capacity compared with a “propensity score-matched external control”.
The results have yet to appear in the peer-reviewed literature, and some experts have urged caution in their interpretation, particularly with regard to the use of external historical control groups and the small number of patients (12 have completed the 36-month period). However, uniQure’s data have been widely welcomed as a breakthrough for a field that has experienced its fair share of false starts (most recently Roche/Ionis halting of its phase 3 dosing of tominersen in 2021 after promising phase 1/2a results). Moreover, the findings have bolstered interest in therapeutic approaches targeting exon 1 in the mutant allele in addition to reducing levels of the full-length huntingtin protein.
Huntington’s disease is a triplet repeat disease in which the huntingtin gene’s exon 1 bears the CAG repeat encoding the polyglutamine stretch that defines the pathology. It’s therefore not surprising that the N-terminal part of HTT and its product have attracted attention as drug targets. Broadly speaking, scientists have tried to get at exon 1 in three ways: targeting the gene itself to block transcription, targeting the mutant mRNA to inhibit translation, and targeting the truncated protein that results from the mutant mRNA. A recent review provides a thorough survey of the preclinical work on these three fronts.
From the drug-discovery point of view, the most advanced programs focus on the development of ASOs or RNAi sequences against the CAG repeat in the mutant mRNA. The motivation behind this strategy is in part the realization that transcription of mutant HTTexon 1 results in a shortened 102 nt mRNA that encodes a toxic protein prone to aggregation: HTTexon1.
To explain what goes wrong in RNA splicing, we need to take a quick detour into the biochemistry of mRNA processing. In any cell, pre-mRNA processing is a competition between the splicing machinery (which removes introns from transcribed genes by recognizing an intronic 5′ splice site, branch point, and 3′ splice site) and the machinery that carries out intronic polyadenylation. Intronic polyadenylation cleaves transcripts within introns and adds a poly(A) tail to the shortened exon–intron fragment transcript when intronic sequences like AAUAAA are present together with a downstream U/GU-rich element.
All of the above is important for Huntington’s because, in healthy brains (specifically the striatum), U1 small nuclear ribonucleoprotein (snRNP) is thought to sit on the cryptic polyA sites in intron 1 of HTT, blocking intronic polyadenylation and enabling accurate splicing of introns and production of a full-length (9,500 nt) mature HTT mRNA. In contrast, in Huntington’s patients, increasingly long CAG repeats in the huntingtin pre-mRNA are thought to sequester U1 snRNP, thereby interfering with formation of the spliceosome complex and making cryptic polyA sites accessible. The result is premature termination of transcription within intron 1, resulting in the generation of the the shortened 120 nt HTTexon1 mRNA transcript that encodes an N-terminal 17-amino acid HTTexon1 protein.
In wild-type huntingtin, components of the spliceosome, such as U1 snRNP make cryptic polyA sites in intron 1 inaccessible to the transcriptional machinery. Accurate splicing ensues, and full-length huntingtin mRNA is produced. In Huntington’s Disease, the CAG repeat is thought to sequester U1 snRNP, exposing the cryptic polyA sites, ultimately leading to the production of HTTexon1. Source: Nature Communications)
Until the UniQure program, most disease-modifying therapies in the clinic have sought to downregulate full-length huntingtin and haven’t discriminated between mutant protein and wild-type protein. The prevailing thinking has been that going after full-length HTT makes sense because both the full-length protein—and fragments of it produced by proteolytic degradation—were likely the main problem.
By targeting exon 1, AMT-130 aims to specifically reduce production of toxic HTTexon1. And several other drug developers have also started to pivot and focus more closely on targeting HTTexon1, with the hope that such approaches might have greater efficacy in reducing huntingtin aggregate nucleation.
Just this year, Alnylam/Regeneron recently took ALN-HTT02 into phase 1b testing. This siRNA is conjugated to a 2′-O-hexadecyl C16 palmitate lipid that enables traversal of the blood brain barrier. It targets a conserved mRNA sequence within huntingtin exon 1, leading to the RISC-mediated degradation of all HTT mRNAs. The approach downregulates both HTTexon1 and full-length HTT — and does not discriminate between the wildtype and mutant alleles.
There are other molecules in development that directly target the expanded CAG repeat in exon 1 that are allele-specific. Vico Therapeutics’ VO659 is an ASO with an allele-preferential mechanism of action, targeting expanded CAG repeats in the mutant transcript and inhibiting translation of the mutant allele via steric block. It is currently in phase 1/2a clinical trials, and the company announced positive interim biomarker data in September 2024.
Meanwhile, in the preclinical space, Sangamo/Takeda are developing a mutant-allele selective approach, focusing on blocking transcription of the huntingtin gene using lentiviral vector delivered zinc finger repressor transcription factors (ZFP-TFs) that target the pathogenic CAG repeat. They have shown that their ZFP-TFs repress >99% of disease-causing alleles while preserving expression of normal alleles in patient-derived fibroblasts and neurons. Lentivirally delivered ZFP-TFs lead to functional improvements in mouse models, opening the door to their potential clinical development.
Haystack is aware of at least three other companies developing therapeutics aimed at reducing the toxic effect of HTTexon1, but details of their programs are scarce. China-based HuidaGene Therapeutics is developing a CRISPR-based gene editing product to fix the mutant allele. Galyan Bio was developing GLYN122, a small molecule directly targeting HTTexon1, but the company seems to have ceased operations. Similarly, Vybion has been developing INT41, a functional antibody fragment against HTTexon1, but its current status is also unclear.
It is sobering that over 150 years’ since the first description of Huntington’s disease, which many think of as the archetypal monogenic disease, that we still lack a definitive understanding of its pathogenic mechanism. We don’t know whether the pathology arises from HTT protein, RNA, DNA or some combination of these. And despite the buzz surrounding HTTexon1, most of the data supporting its relevance to human disease still originates from work in mouse models, which recapitulate only certain aspects of the human disorder. That said, raised levels of HTTexon1 are present in patient brain biopsies, with the longer CAG repeats in individuals with juvenile Huntington’s resulting in higher levels of the truncated transcript.
It will be exciting to follow the progress of UniQure’s AMT-130 as our understanding of where in disease progression, and in which patients, this therapy will be most effective. And beyond HTTexon1, other therapeutics targeting alternative disease pathogenic mechanisms are on the horizon. Last month, Skyhawk Therapeutics reported promising phase 1/2 clinical results for it oral small-molecule splice modifier SKY-0515. Elsewhere, broadening understanding of DNA mismatch repair enzymes and the role of somatic repeat instability in the disease have led to investment in a flurry of startup companies focused on this mechanism. That work is now leading to broader excitement that therapies may become available for other difficult-to-treat triplet repeat diseases like Fragile X syndrome, Myotonic dystrophy type 1 and Friedreich ataxia, as demonstrated by the recent deal between Harness Therapeutics and Ono Venture Investment.
Bilix, recognized as a top Innovator’s Pitch Challenge winner at RESI Boston this past September, is making waves in the biotech space with its innovative multi-modality approach to inflammatory and autoimmune diseases. In this interview, Myung Kim, Founder and CEO, shares how participating in RESI Boston helped the company connect with key investors, refine its strategy, and advance its clinical milestones.
Hear firsthand how Bilix is driving progress in complex disease treatment and discover how your company can join the next generation of innovators pitching at RESI London and RESI JPM. Applications are now open.
By Tony Jones, CEO, One Nucleus (Special Guest Contributor)
ELRIG, Life Science Integrates, Life Science Nation, One Nucleus and SLAS will provide delegates with the opportunity for cross-event partnering during London Bio-Innovation week, which runs 1-5 December, 2025
One Nucleus’ Genesis conference partnering app open to delegates attending any of Bio-Innovation Week events
Initiative to provide extended opportunities for networking, to support the life science ecosystem
London Bio-Innovation week, which runs 1-5 December, 2025, will see each of the five organisations delivering events in the UK’s capital city. While each event is being run independently, collectively their co-location in one city provides a unique opportunity to meet with in excess of 1000 of the brightest science and business minds in London that week.
To further support those seeking new collaborations, insights and opportunities, the event organisers will provide the opportunity for cross-event partnering. Delegates attending any one of the Bio-Innovation Week events will be able to access the One Nucleus Genesis app, to connect with delegates attending different conferences.
Tony Jones, CEO, One Nucleus, said: “Collaboration sits at the core of translating world leading bioscience research into new ventures developing innovative products and technologies to improve patient outcomes. With so much activity in London for Bio-Innovation Week, we identified a unique opportunity to support the life science sector, by opening the Genesis conference partnering app to both attendees and non-attendees, providing a platform for partnering across the multiple events.”
ELRIG are proud to be a leading European not-for-profit organisation dedicated to uplifting the life science and drug discovery community. Our mission is to foster open access to modern research and innovation. Bringing together our vibrant community of over 12,000 life science professionals from academia and biopharma to connect, collaborate and encourage curiosity.
Formed in 2011 by Christopher Watt and Samuel Thangiah, Life Science Integrates (LSI) brings together Senior Leaders from across the Life Sciences, including industry, academia, government and regulators; providing them with unique opportunities to be part of the conversations that set out the industry’s challenges and identify effective strategies and solutions.
The Redefining Every Stage of Investment (RESI) conference series, provided by Life Science Nation, connects start-ups and investors and strategic licensing partners. RESI maximizes fundraising companies’ efforts to find partners who are a fit for their technology and stage of development. RESI is uniquely cross-border and cross-domain, connecting start-ups with 10 categories of global investors across the silos of drugs, devices, diagnostics and digital health. RESI caters to both the earliest stage start-ups, those seeking grants, seed and angel capital, and the early-stage firms who seek series A and B funding. RESI is a unique and powerful tool for sourcing assets and advancing innovation across early-stage life science and healthcare.
One Nucleus is a not-for-profit Life Sciences & Healthcare membership organisation headquartered in Cambridge. We support institutions, companies and individuals in the Life Sciences sector providing local, UK-wide and international connectivity.
The Society for Laboratory Automation and Screening is the global leader in bringing life sciences researchers and laboratory technology providers together under one roof for knowledge sharing and collaboration aimed at transforming research. Annually, SLAS holds its must-attend International Conference & Exhibition in the U.S. and its Europe Conference and Exhibition, with opportunities for start-ups to gain exposure to thousands of potential customers, as well as award opportunities for scientific content by way of poster presentations and the annual Innovation Award. Regular networking events around the world enable regional communities to come together to strengthen research collaboration.
Commercial interest in targeted epigenetic therapies — agents that target specific genes without altering bases in their sequence or causing double-strand breaks or even single nicks in the DNA — continues to grow, as underscored by the latest financing announced by Epigenic Therapies. The unique selectivity and specificity of targeted epigenetic therapeutics offers compelling advantages over small-molecule epigenetic drugs, which target a specific epigenetic reader, writer or eraser, but affect genes across the genome and affect many diverse tissues, leading to narrow therapeutic windows that make them difficult to develop for conditions outside of cancer.
All of these therapies are designed around an alluring set of simple principles: take a gene-specific DNA-binding domain — zinc-finger proteins (ZFPs), ‘dead’ Cas9 (dCas9) with mutations in its RuvC and HNH endonuclease domains, or transcription activator-like effectors (TALEs) — and tether it via an amino acid linker to an enzymatic effector module. This effector is either an enzyme that directly places or removes a specific epigenetic modification (e.g., TET, histone demethylases or the histone acetyltransferase p300) or a transcriptional activator (e.g., VP16) or repressor (e.g., KRAB).
Epigenetic editing approaches have recently focused on dead CRISPR (dCRISPR) domains fused to various epigenetic effectors, but transcription activator-like effectors (TALEs) and zinc finger proteins (ZFPs) also continue to be explored. Source: TINS
A particularly compelling application for such treatments is genetic disorders of haploinsufficiency (like Dravet’s) or imprinting disorders (like Angelman’s or Prader Willi). There are also many of these diseases where the therapeutic genes would be too large (>4.0 kb) for a traditional AAV gene-therapy approach; in contrast, epigenetic editing machinery can be packaged into an AAV vector.
In a first paper published in Nature, the groups of Kevin Bender and Nadav Ahituv at UCSF (scientific co-founders of Regel Therapeutics) sought to test a targeted epigenetic therapy in patients with SCN2A mutations that exhibit decreased NaV1.2 function. These individuals have impaired action potentials, synaptic transmission and manifest diverse neurological symptoms and seizures, with few therapeutic options, beyond symptomatic anti-seizure medications that have a dizzying range of debilitating side effects.
The UCSF teams leveraged conditional genetic knock-in technolgoy or CRISPRa technology — an AAV-delivered SCN2A-promoter-targeting dCas9 fused to a VP16 activator domain — to upregulate transcription of the SCN2A gene. Using either approach, they were able to boost transcript levels from the healthy SCN2A allele, ameliorating electrophsiological deficits and chemical-induced seizure activity in Scn2a+/− mouse models. Importantly, these effects were seen in adolescent mice, which conventionally have been thought to be too old to respond to treatment. This suggests that rescue of normal dendritic excitability with epigenetic agents at later stages of life might be capable of restoring neuronal function, with implications for patients.
In a separate set of experiments, the authors showed that their epigenetic approach was able to rescue neurophysiological activity in haploinsufficient neuron-like cells from SCN2A-knockout human embryonic stem cells. This cross-species reproducibility provides further confidence that CRISPRa-mediated upregulation could be translated into human treatments.
In a second paper in Nature Biotechnology, a team from Epigenic Therapeutics (Shanghai, China) describes the design and validation of optimized epigenetic regulators (EpiRegs) to silence genes in a precise, durable way without altering genomic DNA. Epigen’s Shaoshai Mao and his collaborators at the Chinese Academy of Sciences and the First Affiliated Hospital of Anhui Medical University tested combinations of TALE- and dCas9-based systems, systematically optimizing effector domains and fusion architectures, looking for effective regulators of gene expression. The best-performing variant, EpiReg-T (a TALE-based system, which eliminates the need for a guide RNA), achieved 98% silencing of target genes in mice, substantially outperforming dCas9-based versions.
Using lipid nanoparticles (LNPs) for delivery, a single administration of EpiReg-T in macaques induced long-term repression of the PCSK9 gene, which encodes a validated target for the treatment of hypercholesterolemia. EpiReg-T reduced PCSK9 expression by >90% and LDL-cholesterol by about 60%, with effects persisting for nearly a year (343 days).
Mechanistically, the team used whole-genome bisulfite sequencing and cleavage under targets and tagmentation (CUT&Tag) to show that EpiReg-T induced stable DNA methylation and repressive histone marks at the PCSK9 promoter. The silencing persisted even after liver regeneration and could be reversed by targeted epigenetic activation. Multiomic analysis in mice, macaques and human hepatocytes confirmed high specificity of the manipulation and minimal off-target effects. Overall, these finding, as well as similar results reported in April by Chroma Medicine, establish epigenetic editing as a promising therapeutic platform for durable and reversible gene silencing.
Overall, targeted epigenetic therapies offer clear safety advantages over small molecules that indiscriminately target all genes under the control of an epigenetic eraser or writer enzymes. They avoid the potential risks associated with creating single- or double-strand DNA breaks associated with CRISPR/Cas9 gene, base or prime editing therapies. And they avoid the insertional mutagenesis risks associated with traditional viral gene therapies. What’s more, in applications requiring gene upregulation in haploinsufficient disease, these approaches maintain the endogenous regulatory context of the functional allele. This is in stark contrast to traditional gene-therapy replacement approaches, where overexpression of an introduced therapeutic gene can often lead to toxicities and immunogenecity.
Of course, questions still linger around the persistence of the changes elicited by these epigenetic agents. Will they persist in patients for long periods — for years or even decades? If they can, then epigenetic therapy may offer compliance advantages over small molecules, antibodies, ASOs or even siRNAs, which have treatment durations of six months or less.
Like all genetic medicines, though, delivery remains the key headache. Thus far, AAV vectors, lipid nanoparticles or ribonucleoproteins (RNP) have all been explored to deliver epigenetic therapies (with some evidence that RNPs might have advantages because they can result in higher dCas9 dosages within target cells). For AAV vectors, the fact that targeted epigenetic therapy might only need to be given once might be an advantage in terms of immunogenicity/neutralization concerns against the vector.
A broader point is that the safety profile of targeted epigenetic editors may offer advantages if AAV vectors are used as delivery vehicles: if the epigenetic agents themselves can be delivered at high dosage (given their intrinsic favorable safety profile and presumed maximal tolerated dose), perhaps AAV vector dosages could be lower than current practice. With many current gene therapies requiring dosages of 1013 or more viral particles/kg in patients, it is increasingly becoming clear that unacceptable liver toxicities arise from the virus at these levels in clinical studies. It will be interesting to follow this space as more agents enter human testing.
The firm is focused on therapeutics companies and does not invest in medical devices, diagnostics, or digital health. The firm is open to considering assets of very early stages, even those as early as lead optimization phase. The firm considers various modalities, including antibodies, small molecules, and cell therapy. Currently, the firm is not interested in gene therapy. Indication-wise, the firm is most interested in oncology and autoimmune diseases but has recently looked at fibrotic diseases and certain rare diseases as well.
The firm is opportunistic across all subsectors of healthcare. Within MedTech, the firm is most interested in medical devices, artificial intelligence, robotics, and mobile health. The firm is seeking post-prototype innovations that are FDA cleared or are close to receiving clearance. Within therapeutics, the firm is interested in therapeutics for large disease markets such as oncology, neurology, and metabolic diseases. The firm is open to all modalities with a special interest in immunotherapy and cell therapy.
A strategic investment firm of a large global pharmaceutical makes investments ranging from $5 million to $30 million, acting either as a sole investor or within a syndicate. The firm is open to considering therapeutic opportunities globally, but only if the company is pursuing a market opportunity in the USA and is in dialogue with the US FDA.
The firm is currently looking for new investment opportunities in enterprise software, medical devices, and the healthcare IT space. The firm will invest in 510k devices and healthcare IT companies, and it is very opportunistic in terms of indications. In the past, the firm was active in medical device companies developing dental devices, endovascular innovation devices, and women’s health devices.
A venture capital firm founded in 2005 has multiple offices throughout Asia, New York, and San Diego. The firm has closed its fifth fund in 2017 and is currently raising a sixth fund, which the firm is targeting to be the largest fund to date. The firm continues to actively seek investment opportunities across a […]
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