Regeneron Pharmaceuticals will partner with Parabilis Medicines to discover and develop an initial five candidates encompassing a new form of antibody-drug conjugates aimed at challenging and historically undruggable targets, through a strategic research collaboration that could generate up to $2.3 billion-plus for the Cambridge, MA, biotech.

Regeneron will marry its antibody capabilities with Parabilis’ stabilized helical peptide or Helicon platform, to develop both Antibody-Helicon Conjugates (AHCs) as well as stand-alone therapies based on Helicons—stabilized, cell-penetrant alpha-helical peptides designed to engage intracellular protein targets, including flat surfaces that are not well suited to traditional small molecule binding.

While ADCs traditionally use antibodies to selectively deliver drug payloads into target cells to induce their death from within, the AHCs envisioned by Regeneron and Parabilis would combine antibody-targeted cell access with Helicon payloads designed to selectively modulate specific intracellular proteins, including some long-undruggable proteins.

“In addition to the potential of Helicons to address previously undruggable targets, the collaboration’s intent to couple Helicons to our VelocImmune® derived-antibodies so as to precisely deliver them to cells of interest represents an exciting new approach with the potential to create an entirely new therapeutic class that can span multiple therapeutic areas,” George D. Yancopoulos, MD, PhD, Regeneron’s board co-chair, president, and CSO, said in a statement.

Regeneron has agreed to pay Parabilis $125 million, consisting of a $450 million upfront payment and commitment to invest $75 million in Parabilis’ next equity financing, subject to specified conditions. Regeneron also agreed to pay Parabilis payments tied to achieving development, regulatory, and commercial milestones, as well as tiered royalties up to the low double-digits on future net sales of any approved medicines resulting from the collaboration.

Five initial targets

With five initial targets, the collaboration agreement could generate up to approximately $2.2 billion in total milestone payments to Parabilis.

Under the terms of the agreement, additional targets may be pursued upon additional option payments from Regeneron.

Regeneron shares fell nearly 10% Monday, to $629.68, from Friday’s close of $698.25, and plateaued on Tuesday, inching up 0.1% to $630.30. The Monday drop reflected not the Parabilis deal but a clinical setback: Regeneron on Friday evening acknowledged the failure of a Phase III trial (NCT05352672) assessing two dose levels of the lymphocyte-activation gene-3 (LAG-3) inhibitor fianlimab in combination with a PD-1 inhibitor, Regeneron’s marketed drug Libtayo® (cemiplimab), as a first-line treatment for patients with previously-untreated, unresectable locally advanced or metastatic melanoma.

Fianlimab plus cemiplimab failed the trial by not reaching statistical significance for the primary endpoint of improvement in progression-free survival (PFS) compared to monotherapy with another PD-1 inhibitor, Merck & Co.’s Keytruda® (pembrolizumab), the multi-indication cancer immunotherapy, Regeneron said, in an announcement released more than four hours after the close of financial markets.

Parabilis, a privately held company which rebranded from FogPharma in 2024, rang in 2026 by announcing the closing of a $305 million Series F financing on January 8, with proceeds intended to support continued clinical development of its lead helicon peptide candidate zolucatetide (formerly FOG-001)—a first and only direct inhibitor of the elusive β-catenin:TCF interaction, according to the company—including progression toward a registrational trial in desmoid tumors and continued evaluation across genetically simple and more complex tumor types.

Positive preliminary data

In March, Parabilis presented preliminary clinical data at the 11th Biennial Meeting of the International Society for Gastrointestinal Hereditary Tumors (InSiGHT) showing significant improvement in duodenal polyposis at 60 weeks in a patient with familial adenomatous polyposis (FAP) treated with zolucatetide in the company’s ongoing Phase I/II trial (NCT05919264).

The patient showed a 52.2% reduction in desmoid tumor diameter, as well as “substantial” reductions in polyp number and size compared with a pre-treatment evaluation nearly two years prior, consistent with downstaging from Spigelman stage II to stage I.

The financing, Parabilis added, will also support advancement of its targeted discovery pipeline, including its prostate cancer franchise, and additional efforts to leverage the company’s Helicon platform to unlock long-undruggable disease targets.

In addition to zolucatetide, Parabilis’ pipeline includes:

• Two prostate cancer-fighting discovery phase programs, an ERG degrader Helicon program, and an androgen receptor degrader
• A beta-catenin degrader Helicon program targeting mutations in the Wnt/β-catenin pathway, linked to 80–90% of cases of colorectal cancer, that is also in discovery phase
• A Helicon-enabled alpha radioligand therapies (HEARTs) program against multiple cancer targets, a program partnered with ARTBIO, in hit identification phase.

“Through our own pipeline, we have demonstrated the potential of Helicon peptides to directly inhibit or degrade several disease-driving proteins in oncology that have long been considered out of reach,” stated Mathai Mammen, MD, PhD, Parabilis’ chairman, CEO, and president. “We are thrilled to enter into a collaboration with Regeneron that builds on this foundation, combining the intracellular access and binding capabilities of our Helicons against challenging targets with antibodies from Regeneron.”

The post Regeneron, Parabilis Ink Up-to-$2.3B Antibody-Peptide Conjugate Collaboration appeared first on GEN – Genetic Engineering and Biotechnology News.