Solstice Oncology has secured $225 million in series A funding to advance a next-gen immunotherapy that the biotech hopes will turn “darkness to light” for cancer care.
The company licensed the Fc-enhanced cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, called porustobart, from China's Harbour BioMed back when Boston-based Solstice was founded in February. In return for a $105 million upfront package, Solstice can develop and commercialize the drug outside of China and has already taken porustobart into phase 2 development for microsatellite stable (MSS) stage II and III colon cancer.
Solstice noted in its Sept. 9 release that this patient population has “yet to benefit from immunotherapy.”
The series A—led by RA Capital Management and featured the likes of Canaan Partners and Forbion—will fund the phase 2 trial testing porustobart with Keytruda. The study is due to start enrolling this year for a readout in the second half of 2027. Solstice also plans to develop porustobart in another, as-yet-undisclosed indication.
MSS colon cancer is a cold tumor, meaning the tumor doesn't trigger a strong immune response and isn't impacted by most immunotherapies, with the standard of care consisting of surgery and chemotherapy. Solstice’s molecule is designed to work with and widen the response of PD-1s like Keytruda by releasing a second brake on the immune system and depleting the immunosuppressive regulatory T cells that shield tumors from attack.
By pairing porustobart with Keytruda, Solstice CEO Caroline Loew, Ph.D., told Fierce that the company is aiming for a “synergistic response” that is especially effective in MSS colon cancer.
“We know that an anti-PD-L1 by itself has a 0% response rate in this setting,” Loew explained in an interview. “PD-L1 plus first-generation CTLA-4 is about up to 5% in this setting.”
“If we add our treatment, we're seeing responses at 30%,” said Loew, referencing Harbour’s phase 1b trial for the porustobart, where patients stayed in remission (PDF) for an average of 8.4 months.
“There's a big difference by putting the two together, so you want to use all of the mechanisms you can to your advantage,” the CEO added.
Porustobart is also being designed with a shorter half-life than existing treatments—four to five days compared to roughly two to three weeks for existing CTLA-4 antibodies—which Solstice believes can make dosing more flexible, reducing the frequency and duration of immune-related adverse events.
“We're essentially unlocking this potential of CTLA-4 to be practice-changing, and that's a huge deal,” Loew said. “The first generation of immunotherapy had incredible outcomes for patients, and we're taking that next step of opening up the aperture for more patients to have access to immunotherapy.”
In addition to being designed as a unique second-generation CTLA-4 antibody, porustobart is also going to be administered in the neoadjuvant setting, before any surgical intervention.
“At that point, your immune system is intact,” Loew said. “You haven't developed any resistance, and the tumor itself is visible to the immune system. If you can eradicate that micrometastatic disease, that's where you drive cure,” the CEO added.
Anti-CTLA-4 checkpoint inhibitors have proven their worth in oncology in the form of Bristol Myers Squibb’s blockbuster Yervoy and AstraZeneca’s Imjudo. Yervoy is approved for unresectable or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer, although immune-mediated toxicities give the antibody a narrow therapeutic window.
Solstice isn't alone in aiming a CTLA-4 inhibitor specifically at colon cancer. Agenus is preparing to take a combination of its CTLA-4 inhibitor botensilimab and its anti-PD-1 antibody balstilimab into a phase 3 study for patients with MSS colon cancer, a market that Agenus said could be worth $7 billion in the U.S. alone.
Loew said that the name Solstice represents a turning point and a moment of transformation from darkness to light for cancer care, although she noted that “most things fail” and has the experience to prove it. She previously led Mural Oncology, which spun out of Alkermes with $275 million in 2023. Two years later, Mural laid off 90% of its staff after its IL-2 variant failed its phase 3 trial, and Mural was purchased by Xoma Royalty last year.
Loew, whose career also included a stint as head of R&D strategy and planning for BMS, told Fierce that she was drawn back into the biotech startup world because of her belief in porustobart's mechanism, backed up by clinical data with “responses that haven't been seen before” and the potential to use the therapy in a neoadjuvant setting.
“When you put those three things together, you're like, ‘Wow, this is de-risked, and there's a potential to make a big difference in what's a very underserved population,’” she said.