The Needle Issue #22


Happy belated New Year from The Needle, a newsletter from Haystack Science to help you navigate the latest translational research, with a roundup of the latest news on preclinical biotech startups from around the world.

With the scramble to get announcements and deals before the biotech schmoozefest JP Morgan, it’s been a busy start to January. In terms of translational research, scientists from Ikena Oncology (now Imagene Bio) Espervita Therapeutics, Scripps spinout Abide Therapeutics (now Lundbeck), Kayothera and Japan’s C4U Corporation published papers describing discovery science. Given the more upbeat fundraising environment, seed, series A and series B financings have been ticking over rapidly since the beginning of January, with strategic funds Boehringer Ingelheim Ventures and Pfizer Ventures participating in multiple financings. Novo Nordisk Foundation also set aside a massive $856 million in funding for early-stage European startups. In the week before JPM, a whopping 19 preclinical deals were announced. Prominent multinationals with 2 or more deals each included Boehringer Ingelheim, Pfizer, Eli Lilly, and Novartis. As usual, anything we missed in the biotech startup world, let us know (info@haystacksci.com).

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As is customary at the turn of the year, we have taken the opportunity to take a look back at financing deals we covered since issue#1, which went live in April last year. Together, these data offer a snapshot of how capital flowed into early-stage, preclinical therapeutic startups in 2025 — and where it did not.

Before diving into the numbers, it is worth qualifying that this analysis captures only publicly disclosed financing rounds, rather than the full universe of early-stage biotech funding. An increasing fraction of preclinical companies now operate in stealth, in part because of fast-moving competition from regions such as China. As a result, the figures presented here likely undercount the true level of early-stage activity.

From the start of our coverage in Q2 2025 through the end of December, we reported 195 preclinical financing rounds. Because Haystack Science focuses on discovery-stage and pre-IND companies, this number excludes financings for assets already in clinical development. Even so, the dataset provides a useful lens on early-stage investor behavior.

Independent industry analyses paint a consistent picture. Multiple sources indicate that 2025 was a year in which venture capital shifted toward later-stage, clinical-stage deals, which were fewer in number but larger in size. This trend was reinforced by ‘Q4 2025 Biopharma Licensing and Venture Report’, presented at the JP Morgan conference. According to JP Morgan, 2025 saw just 191 seed and Series A financings, the lowest total since 2020.

According to the Haystack Science data sample, no venture fund made a series A investment in more than three companies last year (these series A financings ranged from $8–300 million, with a median of $42.5 million). As the deals that Haystack tracks are only the publicly disclosed subset, we expect our sample is skewed to companies that raised larger sums. In the deals we tracked, the most bloated series A ($300 million) went to Cambridge, Mass.-based Lila Sciences, a generative ML model powered startup building “autonomous, closed-loop experimentation using generative ML models to generate drug mechanism hypotheses, test them robotically in the lab with minimal human intervention, and iteratively learn from results.” Lila was backed by megafund Flagship Pioneering and General Catalyst.

21 funds invested in more than one series A round. These were: Arch Ventures, Atlas Venture, Lightstone Ventures, 3E Bioventures, Access Industries/Biotechnology, BGF, BVF Partners, Canaan Partners, Cormorant Asset Management, Dementia Discovery Fund, Eight Roads, Johnson & Johnson Innovation – JJDC, Khosla, Omega Funds, Orbimed, Polaris Partners, Samsara, Santé Ventures, Sofinnova Partners, The Column Group, and Versant Ventures. No fund invested in more than 3 series A investments in last year’s sample.

Further back in the pipeline, we tracked 60 deals. These seed financings—which ranged from $1.1–54.5 million with a median of $10.45 million—were mostly for smaller amounts ($1–$30 million), with a few much larger financing amounts. Overall, 85 different funds, family offices, angels and individuals participated in funding preclinical therapeutic startups in 2025. Of these 85 sources of financing, only 7 financed more than one company. The takeaway from this is that most (>90%) of companies at the seed stage receive funds from a completely unique set of investors.

The 7 financing entities involved in more than one seed deal were: AdBio Partners, Kurma Partners, NRW Bank, Ackermans & van Haaren (AvH), Bioinnovation Institute (BII), ClavystBio and ExSight Ventures. It is noteworthy that two of these funds are based in Paris, France: AdBio Partners and Kurma Partners. AdBio specializes in early-stage investments across Europe with a ~€86 million ($102 million) fund raised in 2021 focusing on oncology, immunology, and rare diseases. Kurma is part of the Eurazeo group, managing >€600 million in assets across several funds focused on early-stage therapeutics and diagnostics.

NRW.BANK, based in North Rhine-Westphalia, Germany, invests in innovative biotech companies focusing on tech-driven healthcare, bio-digital integration, and novel platforms for data/discovery, aligning with broader innovation goals. They appear to be an important source for the small scattering of financing (13) deals in German-speaking countries. NRW works closely with AvH, an Antwerp, Belgium-based diversified holding company and investment firm, with AvH Growth Capital a proactive investor in early-stage companies like DISCO Pharmaceuticals and Evla Bio.

Another very interesting seed funder is BII in Copenhagen Denmark. The institute provides in-kind grants of up to €3 million for bridging translational studies in European academic institutions. For those projects that progress to a company build, a combination of convertible loans of €500K (Venture Lab) and then €1.3 million (Venture House) are made available to complete seed funding. As of January 2026, BII has supported over 130 early-stage life science and deep tech companies, with many attracting significant external funding. This month, there was news that Novo Nordisk has just plowed another $856 million of funding into BII.

Overall, in terms of the location of where most investment is occurring, our analysis reveals the capacity to host startups is expanding across the globe, with at least 19 countries hosting one preclinical startup that received funding in 2025. These countries were: USA, UK, France, Switzerland, China, The Netherlands, Canada, Denmark, Germany, Belgium, Japan, Spain, Israel, Australia, Ireland, Norway, Portugal, South Korea and Singapore. Perhaps the prominence of France as a location for preclinical therapeutic startups was most surprising from our sample. Interestingly, a lot of ex-US startups now also have a US (usually Cambridge, Mass.-based) headquarters. Digging deeper, 85 different cities around the world host a startup that obtained financing (pre-seed to series B) in 2025, with 20 cities hosting two or more. As expected, the Boston cluster led with 28 preclinical therapeutic startups, the Bay area hosted 19, and the UK’s Golden Triangle had 13. Of the following pack, some interesting standout cities were Paris, France (with 5 in our sample) and New York City (with 7), the latter long in the shadow of its Boston neighbor.

In terms of the disease areas attracting early-stage investor money, cancer dominates, comprising the focus for 34.4% of the funding raises. This is slightly lower than the biopharma sector as a whole, where cancer comprises up to 45% of pipelines. Following cancer, neurodegenerative disease, autoimmune disease and inflammatory disease all figured prominently. The uptick in deals for companies tackling CNS disorders has been a rolling theme recently, given the burden of neurodegenerative disease and dementia on public health systems and the paucity of disease-modifying treatments. With the continuing stampede around GLP-1s/incretins, there was also a healthy number of metabolic/ endocrine disease startups financed.

One last area we looked at was the type of therapeutic being financed by investment groups. Here again, the pharmaceutical industry’s traditional workhorse, the small molecule, remained pre-eminent in 2025, comprising 24% of financing deals in pre-seed, seed, series A and series B financings that were in the preclinical stage. Established modalities like monoclonal antibodies (mAbs) were a common focus. And there was a resurgence of interest in recombinant proteins and peptides (likely boosted by the focus on incretins and the metabolic disease and obesity space). Of new modalities, antibody-drug conjugates, bispecific and multispecific antibodies, antisense oligonucleotides (ASOs), small-interfering RNAs (siRNAs) and chimeric antigen receptor (CAR) immune cell (T cell and NK cells) also were to the fore, each making up around 6% of all the early-stage deals we tracked. A type of therapeutic gathering increasing attention is clearly the induced-proximity therapeutic sector (including the different flavors of PROTACs, DUBTACs and molecular glues). Finally, although a great deal has been mentioned about investor apathy for gene editing and gene therapy, these also captured 3-4% of the deals.

Translational papers: Best of the rest

Target biology

p53 inactivation drives breast cancer metastasis to the brain through SCD1 upregulation and increased fatty acid metabolism | Nature Genetics

Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica | JCI

A glycolytic shunt via the pentose phosphate pathway is a metabolic checkpoint for nervous system sensory homeostasis and axonal regeneration | Cell

Sphingosine kinase 1 is integral for elastin deficiency-induced arterial hypermuscularization | Nature Cardiovascular Research

Endometrial stromal cell-derived TMAO sustains decidualization to prevent recurrent spontaneous abortion | Cell Metabolism

USP25 inhibition ameliorates Parkinson’s disease by restoring mitophagy | PNAS

Extracellular BRICK1 drives heart repair after myocardial infarction in mice | Science Translational Medicine

k5-mediated microglial ferroptosis drives ischemic white matter damage via the Nfatc4–Clptm1l axis | PNAS

Hepatokine fibrinogen-like protein 1 drives liver-kidney crosstalk to promote renal fibrosis | Nature Communications

A GDF-15–GFRAL axis controls autoimmune T cell responses during neuroinflammation | Nature Immunology

Endothelial cell–released CD93 contributes to podocyte injury in idiopathic nephrotic syndrome | Science Translational Medicine

Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis | JCI

LDL-binding IL-10 reduces vascular inflammation in atherosclerotic mice | Nature Biomedical Engineering

Ikena Oncology’s molecular glue IK-595 has antitumor activity on RAS/MAPK pathway-altered cancers | Nature Cancer

Selective disruption of RORγt-CBFβ interaction by IMU-935 prevents RORγt-dependent Th17 autoimmunity but not thymocyte development | JCI

Espervita Therapeutics reports that dual inhibition of ACLY and ACSS2 by EVT0185 reduces steatosis and fibrosis in mouse models of MASH | Cell Metabolism

Abide Therapeutics team shows that inhibition of peripheral diacylglycerol metabolism results in pain suppression | Cell Chemical Biology

Dual FAK and EPHA2 targeting by brigatinib tackles PARP inhibitor adaptive survival response in high-grade serous ovarian cancer | Science Translational Medicine

Combined inhibition of FACT and BET disrupts transcription to suppress tumor growth in mouse models of diffuse midline glioma | Science Translational Medicine

Cancer immunotherapy

Uridine depletion impairs CD8⁺ T cell antitumor activity through N-glycosylation | Cell Metabolism

Extracellular GPX4 impairs antitumor immunity via dendritic ZP3 receptors | Cell

Engineering PD-1 and FZD8 -decorated exosome activators of T cells to target immune checkpoint inhibitor-resistant metastatic melanoma | Nature Biotechnology

Targeting autocrine retinoic acid signaling by ALDH1A2 inhibition enhances antitumor dendritic cell vaccine efficacy, according to a team involving scientists from Kayothera | Nature Immunology

CAR-adapted PIK3CD base editing enhances T cell anti-tumor potency | Nature Cancer

Engineered outer membrane vesicles enhance solid tumour CAR-T cell therapy | Nature Biomedical Engineering

CDK10 suppresses nucleic acid sensors-mediated antitumor immunity | Nature Cancer

Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity | Cancer Cell

Targeting the N-acetyltransferase 10/DKK2 axis enhances CD8+ T cell antitumor activity in colorectal cancer models | JCI

Platforms, delivery, editing

Effective combinatorial antifungal therapy using a host defense peptide mimic that self-assembles into delivery micelles | Nature Biotechnology

A team including scientists from Japan’s C4U Corporation report that CRISPR–Cas3-based editing for targeted deletions in a mouse model of transthyretin amyloidosis | Nature Biotechnology

Small intracellular vesicles outperform small extracellular vesicles in uptake, drug delivery and retinal neuroprotection | Nature Biomedical Engineering

Nanoparticles hijack calvarial immune cells for CNS drug delivery and stroke therapy | Cell

Startup news

The new year brought several new venture fund raises:

Osage University Partners, BioNTech, and UPenn Launch $50 Million Seed Fund To Back Penn Life Science Startups

Say what? A16Z raises a whopping $15 billion fund with $700 million assigned for Bio + Health

Arkin Capital closes $100M biotech fund

Lux Capital raises $1.5 billion broad Fund IX set focused on new science, with portion devoted to biotechs

In the seed stage universe, Novo Nordisk Foundation committed $856 in funding for Danish life science incubator BioInnovation Institute

Elsewhere, a new funding collaboration between UKRI Innovate UK and the National Research Council of Canada Industrial Research Assistance Program (NRC IRAP) gave out grants to Chromatin Bio (which is developing a platform synthetic promoter platform for protein expression), Mediphage (which is developing backbone free DNA minivectors), and the Entos Fusogenix PLV (which is developing a cell-type selective fusogenic lipid nanoparticles using Fusion-Associated Small Transmembrane (FAST) reovirus proteins).

In other venture news, some other interesting tidbits:

Deerfield venture fund collaborates with AI biotech Relation Therapeutics to ideate new builds:

Venture finally speaks up about corrosive federal policy as Flagship Pioneering calls out science attacks

Atlas Principal Aimee Raleigh does some crystal-gazing into 2026, with a look at loss of exclusivity cliff facing pharma and a comparison with M&A activity of the major players in 2025

Staying with the rare disease world, a new public benefit corporation was announced that aims to solve the commercialization issues plaguing cell and gene therapies using a combination of risk pooling and infrastructure orchestration of clinical, manufacturing and distribution expertise:

ASGCT, OTXL partner to commercialize stalled rare disease therapies

A new report from dealroom summarizes university spinout activity in Europe

Finally, CRO OH2 announces Kickstarter program and invites new round of applications for US small molecule therapeutic startups in 2026

Preclinical funding

Preclinical deals

Stay in touch

We hope you enjoyed this issue of The Needle and hit the button below to receive forthcoming issues into your inbox

If you’re interested in commercializing your science, get in touch. We can help you figure out the next steps for your startup’s translational research program and connect you with the right investor. Follow us on X, BlueSky and LinkedIn. Please send feedback; we’d love to hear from you (info@haystacksci.com).

Until next week,

Juan Carlos and Andy

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