The question of whether Rubius Therapeutics Inc. would disclose data with its cellular therapy, RTX-240, ahead of the American Association for Cancer Research (AACR) meeting next month was answered in a market-satisfying way as the Cambridge, Mass.-based firm rolled out positive findings from the ongoing phase I/II experiment.

Shares (NASDAQ:RUBY) closed at $30.29, up 84%, or $13.86, after trading as high as $38.71, with investors reacting to partial responses (PRs) in metastatic anal cancer and metastatic uveal melanoma, with no dose-limiting toxicities or grade 3 or 4 adverse events (AEs). RTX-240 emerged from the Rubius platform called Red, which generates red blood cells and genetically engineers them. The compound is an allogeneic, off-the-shelf product that simultaneously presents hundreds of thousands of copies of the co-stimulatory molecule 4-1BB ligand and IL-15TP (trans-presentation of IL-15 on IL-15R alpha) in their native forms. Rubius’ approach is meant to stimulate the immune system by activating and expanding NK as well as memory T cells.

“We’re still optimizing the dosing schedule,” CEO Pablo Cagnoni said during a conference call. “It’s early days.” Even so, Chief Medical Officer (CMO) Christina Coughlin noted that “aspects of dose response have turned up,” with grade 2 AEs appearing at higher doses. “We see a similar pharmacodynamic [PD] effects in both of these [PR] patients,” she added, with activation of NK and T cells. “We’re doing a group of different analyses – the NK signature is one of them, and as we get further, deeper into 2021, we’ll release the full clinical development plan that will include plans for the dose-expansion cohorts.” Meanwhile, Jefferies analyst Michael Yee said in a report that the outcome of the trial as known so far “meets or exceeds [the] higher end of expectations.”

Pablo Cagnoni, president and CEO, Rubius

Five dose cohorts were completed at the time of the data cutoff on Feb. 28, 2021, with 16 patients evaluable for safety (the primary outcome measure) and 15 evaluable for efficacy (the secondary outcome measure) based on RECIST v1.1, as the study continues to enroll. RTX-240 generated a confirmed PR with a 54% reduction in the target lesions at the 1e8-dose administered every four weeks in a patient with metastatic anal cancer whose disease had progressed on anti-PD-L1 therapy. Treatment was ongoing eight months following the first dose at data cutoff.

In the uveal melanoma patient, the drug yielded an unconfirmed PR with complete resolution of the target hepatic lesion and resolution of 14/15 hepatic lesions at the 1e10-dose administered every four weeks. The subject’s disease had progressed on anti-PD-1 therapy, and treatment was ongoing four months following the first dose at data cutoff.

Stable disease (SD) was seen in six patients, including four with SD for at least 12 weeks. Of those four, a non-small-cell lung cancer patient had disease stabilization for 12 weeks, with treatment ongoing as of the data cutoff. One with soft tissue sarcoma had SD for four months. A pancreatic cancer patient’s disease stabilized for three months, and one with prostate cancer maintained SD for four months. Biopsy data supported the mechanism and biology of the approach, with an increase in trafficking of T and NK cells to the tumor microenvironment, Rubius said. The most common treatment-related grade 1 or 2 AEs were fatigue, chills, nausea, decreased appetite and arthralgias all reported in three patients each.

Immunocore late-stage in uveal

J.P. Morgan analyst Jessica Fye asked about the single grade 1 event of liver toxicity that Rubius reported. Coughlin said it surfaced in the uveal melanoma patient at the 1e10-dose level, given every four weeks. The effect was “transient – lasted one week – and required no management,” she said.

Cagnoni looked ahead to the poster presentation due at AACR. “We expect to be able to get a little bit deeper into some of the details of the PD data at that time,” he said. Rubius also aims to kick off an anti-PD-1 combo trial in the second half of the year.

Guggenheim’s Michael Schmidt wanted to know how the phase II dose might be selected, whether by using PD markers or other factors. He pointed to the biomarker strategy and said the company seems to be “selecting patients that already have activated NK cells at baseline.” Cagnoni said that, “by definition phase I solid tumor trials have a heterogeneous patient population, but we’re going to look at all the data together to make a determination,” including safety, efficacy and PD findings. CMO Coughlin said the firm is “actually not seeking diseases where patients would have activated NK cells,” and is relying on the drug to do that. “Some human tumors will express on their cell surface some of the ligands that would interact with the receptors that RTX-240 is essentially inducing.”

Metastatic uveal melanoma is an especially wicked form. Immunocore Holding plc, of Oxfordshire, U.K., is expected to submit a BLA for tebentafusp for the front-line treatment of the disease in the third quarter of this year, followed by an EMA filing. J.P. Morgan’s Fye, in a March 2 report, said that “with its proven ImmTAX platform, we see tremendous potential for value creation over time as Immunocore applies its technology toward additional cancer targets and other therapeutic areas.” ImmTAX prospects can redirect T cells toward diseased cells by targeting proteins uniquely expressed inside a cell that are presented on the surface via the HLA complex.