Cure
The rare disease sector is growing, and investors are paying attention. Sergey Jakimov, founding partner of LongeVC and serial entrepreneur, credits both the biology and the economics. Rare diseases are, by definition, genetically and mechanistically tractable. "You usually know the gene, you know the protein, and you know the patient. When a modality finally catches up to the biology, such as AAV gene therapy, ASOs, siRNA, base and prime editing — you can move from target ID to a clinical hypothesis in a shorter time span," he said.
The economics are just as compelling. Big Pharma has roughly $180 billion in patent cliff exposure over the rest of this decade, and that math, Jakimov noted, "doesn't care whether you call your target 'rare' or 'common.'" "Pharma needs de-risked, clinically validated assets, and rare disease programs tend to show up better in diligence—clearer endpoints, smaller trials, engaged patient communities, and a higher likelihood of approval from Phase I," he said. The BioMarin-Amicus deal earlier this year was almost a $5 billion advertisement for that thesis.
Investor attention is concentrated in three buckets. The first is rare neurodegenerative diseases: Huntington's, ALS, pediatric neurodegeneration. "Genetic medicines aimed at these are producing real human data, and that's the area with the most overlap into our own longevity and age-related disease focus, so we see a lot of it in our deal flow," Jakimov said. The second is rare oncology, especially pediatric and adolescent indications and genetically defined adult tumors. The third is enabling technologies: AI-driven target discovery, repeat-dose AAV, smarter delivery, and the clinical infrastructure that makes small trials more workable for regulators. "That third bucket is what makes the first two investable at scale," he said.
Over the next five years, Jakimov predicts rare diseases will stop being a category and become the default model for how biotech does innovation. "Orphan therapies are already projected to be roughly a fifth of global prescription revenue, and that's before the gene-therapy economics get unlocked," he said. The companies that win, in his view, will be platform companies—one technical chassis, 10 or 20 rare indications stacked on top—looking more like pipeline machines than single-asset biotechs.
AI will accelerate that shift by compressing two longtime bottlenecks: finding the patient and finding the target. "Genomic screening at the population level is going to surface diagnoses that today take families seven years and a dozen specialists to receive," Jakimov said. "That alone changes the addressable market for every rare disease asset on the planet."
As rare disease programs continue to demonstrate scientific, regulatory, and commercial viability, venture investors are increasing their exposure. Below are eight firms actively investing in startups developing therapies and enabling technologies for rare diseases.
1. OrbiMed Advisors
Stage focus: Seed through public Check size range: $10M–$50M average per venture round Healthcare focus: Biopharmaceuticals, rare disease, oncology, medical devices, diagnostics, and healthcare IT Geographic focus: Globally, including across North America, Asia, and Europe Assets under management: Over $17 billion Currently deploying: Yes Notable healthcare portfolio companies:
Crinetics Pharmaceuticals - endocrine disease therapeutics
Mereo BioPharma - rare disease biopharma
Headquartered in New York City, OrbiMed Advisors is a leading global healthcare investment firm. The firm was originally founded as Mehta & Isaly back in 1989 and later rebranded as OrbiMed Advisors in 1998. Its portfolio ranges from early-stage startups to growth equity, and has included hundreds of biotech, medical device, and healthcare startups across the globe.
2. 5AM Ventures
Stage focus: Seed and Series A Check size range: $100K - $5M Healthcare focus: Biopharmaceuticals, rare disease, drug delivery, and life science tools Geographic focus: Based primarily in Boston and San Francisco, and invests in North American companies Assets under management: $2.2 billion in capital raised as of 2025; assets under management ~$1 billion Currently deploying: Yes Notable healthcare portfolio companies:
Crinetics Pharmaceuticals - endocrine disease therapeutics
Entrada Therapeutics - intracellular delivery of biologics and genetic medicines
Mendra - AI-enabled rare disease drug development and commercialization platform
Founded in 2002, 5AM Ventures primarily invests in seed and Series A startups, with an emphasis on pre-Series A incubation and company building. What sets 5AM Ventures apart from other VCs is its hands-on approach. For example, it’s common for partners to take on short-term operating roles and build startups from the ground up.
3. RA Capital Management
Stage focus: Series A through crossover (pre-IPO); also invests in public biotech Check size range: $500K-$75 million Healthcare focus: Biopharmaceuticals (oncology, immunology, and neurology), rare diseases, metabolic and cardiovascular conditions Geographic focus: Invests globally, with a strong focus on North American companies Assets under management: Over $14 billion Currently deploying: Yes Notable healthcare portfolio companies:
Disc Medicine - rare hematologic diseases
Rhythm Pharmaceuticals - rare genetic obesity disorders
Ascendis Pharma - rare endocrine disorders
Based in Boston, RA Capital Management is a healthcare-focused investment firm specializing in life sciences, biotechnology, and related healthcare technologies across both public and private markets. The VC also has an in-house incubator called Raven Healthcare Incubator, where it builds startups from scratch. RA Capital Management’s portfolio is extensive, with an overarching theme of improving life quality and longevity.
4. Versant Ventures
Stage focus: Pre-seed to series A Check size range: $100K - $5M Healthcare focus: Rare disease, oncology, neurology, immunology, cell and gene therapy, protein engineering. Geographic focus: Invests in life sciences hubs across the U.S., Canada, and Europe Assets under management: $2.4 billion Currently deploying: Yes Notable healthcare portfolio companies:
Jazz Pharmaceuticals - rare sleep disorders, narcolepsy, and epilepsy
Dayra Therapeutics - rare neurological disease
Jade Biosciences - autoimmune disease therapeutics, including IgA nephropathy programs
Versant Ventures is headquartered in San Francisco, with additional offices in San Diego, New York, Vancouver, and Basel. In addition to investing in startups from seed through Series B, Versant Ventures also runs in-house Discovery to build and incubate biotech startups. The firm has an impressive exit rate, with more than 130 exits to date.
5. Flagship Pioneering
Stage focus: Internal company creation (venture building), spanning ideation through Seed/Series A formation and growth-stage scaling Check size range: $500K - $15M Healthcare focus: Platform biotech, mRNA, synthetic biology, rare disease, immunology, and AI-driven drug discovery Geographic focus: Headquartered in Cambridge, MA; invests primarily in North American companies Assets under management: $14 billion (as of July 2024) Currently deploying: Yes Notable healthcare portfolio companies:
Moderna - mRNA therapeutics and vaccines, including rare disease programs
Seres Therapeutics - microbiome therapeutics
Generate Biomedicines - AI-enabled protein design and biologic therapeutics
Unlike some other venture capital firms, Flagship Pioneering incubates internally before external Series A rounds. Noubar Afeyan founded the firm in 2000 and since then, it’s launched more than 120 scientific ventures including Moderna and Lila Sciences. In any given year, Flagship Pioneering is working on six to eight different companies.
6. ARCH Venture Partners
Stage focus: Seed and Series A Check size range: $500K - $5M Healthcare focus: Genetic medicine (including cell and gene therapy), oncology, immunology, neurology, rare diseases Geographic focus: Strongest geographic footprint is in the U.S., with additional investments in China and the UK. Assets under management: $12 billion Currently deploying: Yes Notable healthcare portfolio companies:
Beam Therapeutics - base editing for rare genetic disease
Maze Therapeutics - precision medicines for APOL1-mediated kidney disease and other genetically defined disorders
Arbor Biotechnologies - gene-editing therapeutics for rare genetic diseases, including liver and CNS disorders
Founded in 1986, ARCH Venture Partners specializes primarily in early-stage biotech and life sciences startups. In many cases, they co-found startups alongside scientists from leading universities and laboratories. They often invest in high-risk, high-reward companies, and it pays off—ARCH Venture Partners has invested in 45 unicorns so far.
7. Atlas Venture
Stage focus: Seed and Series A and selective series B Check size range: $500K-$1 million Healthcare focus: Genetic medicines, immunology, inflammation, rare diseases, neurology, and oncology Geographic focus: Based out of Cambridge, MA; invests primarily in U.S. companies Assets under management: $2.4 billion Currently deploying: Yes Notable healthcare portfolio companies:
Alnylam Pharmaceuticals - rare disease RNA medicines
Trace Neuroscience - antisense oligonucleotide therapeutics for ALS and other genetically driven neurodegenerative diseases
Renasant Bio - rare kidney disease
Atlas Venture has been around since the 1980s, but has focused primarily on life sciences and biotech investments since around 2014. Like several of the VCs on this list, Atlas Venture often co-founds and/or incubates the companies they invest in through its talent pool of Entrepreneurs-In-Residence (EIRs).
8. Bain Capital Life Sciences
Stage focus: Series B through growth equity, as well as later-stage clinical programs Check size range: From $1 million for seed capital to $100 million for growth equity Healthcare focus: Rare disease, oncology, gene therapy, medical devices, and diagnostics Geographic focus: Offices in the SF Bay Area, New York City, and Boston; investments globally Assets under management: $9.4 billion Currently deploying: Yes Notable healthcare portfolio companies:
SpringWorks Therapeutics - rare tumor and precision oncology (desmoid tumors, NF1-associated tumors)
Angitia Biopharmaceuticals - bone biology and skeletal disease therapeutics
Bain Capital Life Sciences (BCLS) is an investment arm of the global management firm, Bain Capital. BCLS was founded in 2016 and is focused on funding medical innovation. Veering away from traditional venture capital, BCLS targets four investment profiles: Inflection Capital, Growth Capital, Fallen Angels, and Transformation at Scale.
