A San Diego biotech that goes looking for cancer targets where nobody else can see them - inside the living tumor itself.
A cancer cell, lit up yellow under the microscope. Somewhere on its surface sits a receptor most drug hunters walked past. MBrace built a whole company around the ones that let an antibody in.
Here is a slightly uncomfortable fact about antibody-drug conjugates, the class of cancer drugs everyone in oncology is currently excited about: the hard part was never really the drug.
An antibody-drug conjugate, or ADC, is a fairly elegant idea. You take an antibody - a protein that recognizes something specific - and you chemically staple a toxic payload onto it. The antibody finds a cancer cell, latches on, gets pulled inside, and delivers the poison where it does the most damage and the least collateral harm. Enhertu, Adcetris, Trodelvy: the format works, and the market has noticed. The trouble is that an ADC is only as good as the thing it aims at. The antibody has to find a target that is on cancer cells and not on healthy ones, that is actually reachable in a living body rather than buried out of view, and that obligingly drags the antibody inside the cell after binding. Miss any one of those three and you have spent a great deal of money building a guided missile pointed at nothing.
Most ADC programs get around this by crowding onto a short list of validated targets - HER2, TROP2, a handful of others - and competing on payload chemistry and linker cleverness. It is a reasonable strategy and also a very crowded one. MBrace Therapeutics, founded in 2020, decided to compete somewhere else entirely: on the targets themselves. Its bet is that the antigens worth aiming at are ones nobody has validated yet, and that the way to find them is to stop screening in a dish and start screening inside the body.
That is the whole idea behind SPARTA, the platform MBrace's scientific founders - Renata Pasqualini and Wadih Arap - developed at Rutgers before co-founding the company with oncologist Isan Chen. SPARTA is an in-vivo antibody selection technology. Rather than testing antibodies against purified proteins on a bench, it screens them in living tumors, letting biology itself do the sorting. What survives the screen is a set of antibodies aimed at targets that are, by construction, cancer-specific, accessible, and internalizing. The three constraints that usually get optimized one at a time get optimized all at once.
"An in-vivo approach that leverages biology to develop targets specific to cancer cells - accessible in the body, and internalizing upon binding."
The lead output of that screen is MBRC-101, a first-in-class ADC targeting EphA5, a receptor tyrosine kinase that turns up in a surprising range of common cancers - breast, non-small-cell lung, colorectal, gastric, pancreatic - and that most developers had passed over. It carries MMAE, a well-understood cytotoxic payload, which is a sensible choice: if you are taking a big risk on a novel target, you do not also want to be taking a big risk on unproven chemistry. In December 2023 the company began dosing patients with advanced, treatment-refractory solid tumors in a Phase 1/2 trial. A second program, MBRC-201, followed into the clinic - same platform, different target.
None of this is cheap, which is where the money comes in. In November 2023 MBrace closed an $85 million Series B led by TPG - through both its life sciences fund and its Rise Fund impact strategy - with Avidity Partners and Cowen Healthcare Investments joining existing backers Venrock and Alta Partners. That brought total funding to roughly $110 million. Investors, notably, were not buying a single molecule; they were buying a method. A platform that can keep generating novel targets is worth more than any one asset it produces, and the syndicate priced it accordingly.
An effective ADC target has to clear three bars at the same time. SPARTA screens for all three inside a living tumor.
The target has to be abundant on tumor cells and scarce on healthy tissue - otherwise the payload harms the wrong cells.
In-vivo screening surfaces antigens that an antibody can actually get to in a living tumor, not just ones that look good on a bench.
On binding, the target must pull the antibody inside the cell so the toxic payload is released where it works.
Proprietary in-vivo antibody selection technology, originating at Rutgers, that screens antibodies inside living tumors to surface novel, druggable ADC targets.
A first-in-class anti-EphA5 ADC with an MMAE payload, in a multicenter trial for advanced refractory solid tumors including breast, NSCLC, colorectal, gastric and pancreatic cancers.
A second clinical ADC in a dose-finding, safety and pharmacokinetic study in patients with advanced refractory solid tumors.
| Round | Amount | Date | Lead / Investors |
|---|---|---|---|
| Series A | ~$25M (pre-B total) | 2020-2021 | Venrock, Alta Partners |
| Series B | $85M | Nov 2023 | TPG (lead), Avidity Partners, Cowen Healthcare, Venrock, Alta Partners |
Board-certified in internal medicine, hematology and oncology with 20+ years running clinical trials. Formerly Chief Medical & Development Officer at Mirati, CMO at Aragon (acquired by J&J), and VP of Tumor Strategy at Pfizer.
Co-inventor of the SPARTA in-vivo antibody selection technology developed at Rutgers, and a pioneer of in-vivo phage display and vascular targeting research.
Co-inventor of SPARTA and long-time collaborator with Pasqualini on tumor-targeting and in-vivo screening science that underpins MBrace's platform.
Chief Scientific Officer. Brings 20+ years at Seagen - the company that pioneered the modern antibody-drug conjugate - which was acquired by Pfizer in 2023.
Isan Chen, Renata Pasqualini and Wadih Arap launch the company around the SPARTA in-vivo antibody selection platform from Rutgers.
Backed by Venrock and Alta Partners, MBrace advances SPARTA and its early ADC discovery pipeline.
Avidity Partners and Cowen Healthcare join existing backers; total funding reaches ~$110M. MBRC-101 begins dosing patients in December; preclinical data shown at SABCS.
MBRC-201 advances into Phase 1/2, Steve Alley joins as CSO, and MBrace presents a Trial-in-Progress poster at the ASCO Annual Meeting.
It is a clinical-stage oncology company that develops antibody-drug conjugates (ADCs) against novel cancer targets, using its proprietary SPARTA in-vivo antibody selection platform.
SPARTA is MBrace's in-vivo antibody selection technology - originating at Rutgers - that screens antibodies inside living tumors to find targets that are cancer-specific, accessible, and internalize upon binding, the traits an effective ADC requires.
MBRC-101 is MBrace's lead candidate: a first-in-class anti-EphA5 antibody-drug conjugate with an MMAE payload, being tested in a Phase 1/2 trial for advanced refractory solid tumors.
MBrace raised an $85M Series B in November 2023 led by TPG, bringing total capital raised to roughly $110M from investors including Venrock, Alta Partners, Avidity Partners and Cowen Healthcare Investments.
The company is headquartered in San Diego, California, with research operations at the Thomas O. Daniel Research Incubator in Summit, New Jersey.