MDNA.TO: Additional Confirmed PR in Phase 1/2 ABILITY Trial of MDNA11
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Update on Phase 1/2 ABILITY Trial
On November 6, 2023, Medicenna (TSX:MDNA.TO) (OTC:MDNAF) announced that updated results from the Phase 1/2 ABILITY (A Beta-only IL-2 ImmunoTherapY Study) trial of MDNA11 were presented at SITC. MDNA11 is the company’s albumin-fused, long-acting, IL-2 agonist that induces strong activation of CD8+ T cells and NK cells, has minimal impact on Treg cells, and reduced toxicity compared to recombinant, human IL-2 (rhIL-2).
The following figure shows the best change in target lesion for patients on ≥ 60 g/kg MDNA11 monotherapy. There have been two partial responses (PRs) and three patients with stable disease (SD).
• One patient who experienced a PR has metastatic pancreatic ductal adenocarcinoma (PDAC; MSI-H). This patient had previously failed multiple systemic therapies and was resistant to immune checkpoint inhibitors. Treatment with MDNA11 resulted in 100% shrinkage of target lesions, however, this complete resolution of two target and one non-target lesions could not be considered a complete response (CR) according to RECIST 1.1 criteria due to the presence of a new lesion that was detected after the patient had returned from a seven-week vacation (during which time no treatment was received). The patient received one cycle of radiotherapy to treat the new lesion and continues on MDNA11 treatment.
• A patient with cutaneous melanoma, who had progressed on dual checkpoint inhibitors, showed a 70% reduction of the target lymph node lesion at Week 12 and is classified as a PR. This patient received a more rapid dose escalation than the first three patients treated in the 90 g cohort (30, 60, 90 g/kg Q2W; previously 30, 30, 90 g/kg Q2W), which is the same dosing schedule that will be utilized in the dose expansion portion of the trial. The rate of tumor shrinkage is particularly encouraging and compares favorably to the PDAC patient who experienced a PR (who was on therapy for 22 weeks prior to a confirmed PR).
• Three metastatic melanoma patients exhibited SD. Two patients have experienced SD for > 20 weeks (acral melanoma) while the other patient has experienced SD for >24 weeks (cutaneous melanoma). The patient with cutaneous melanoma has experienced SD for > 1.5 years and had started in the trial at an MDNA11 dose of 10 g/kg with subsequent dose escalations to 30, 60, and 90 g/kg.
Investors should be aware of additional IL-2 results reported at SITC that included data from Werewolf Therapeutics (WOLF) on their lead IL-2 compound WTX-124, which uses a masking technology whereby IL-2 is specifically released in the tumor microenvironment (TME). At the 12 mg dose (highest dose tested; n=5), the company reported one unconfirmed partial response and results that were consistent with a partial response on a restaging scan for another patient. These data are very encouraging for the IL-2 space, which has experienced a number of setbacks over the past couple of years. While Werewolf’s data is promising, we will be following the results closely to determine how durable they are given that the alpha activity of WTX-124 is still present, thus Treg activation may become an issue.
In regards to safety, MDNA11 has exhibited a favorable tolerability profile as there have been no reports of dose-limiting toxicities (DLTs) and no evidence of vascular leak syndrome. The vast majority (95.6%) of treatment-related adverse events (TRAEs) were of grade 1-2 severity and resolved within 48 hours. The grade 3 TRAEs were mostly transient liver enzyme elevations. There were no reports of grade 4 or 5 events.
Lastly, the following slide shows the pharmacodynamic parameters for MDNA at the various dose levels along with T cell expansion for the 90 g/kg dose. The data show a robust activation of effector immune cells (particularly CD8+ T cells), with minimal impact on the population of immunosuppressive Treg cells.
Conclusion
The ABILITY data continue to show that MDNA11 is well tolerated and the two PRs are particularly exciting, especially in the pancreatic cancer patient as that tumor type is not typically thought to be amenable to immunotherapy. Now that single-agent anti-tumor activity has been shown for MDNA11 (in an advanced patient population), we will be very interested to see how the compound performs in combination with Keytruda. That trial should initiate before the end of 2023. In the meantime, the company is continuing to enroll patients in the monotherapy dose expansion trial, with a focus on patients with melanoma, non-melanoma skin cancers, and MSI-H/dMMR tumors. With no changes to our model our valuation remains at $9.00 per share.
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