Positive results from the pivotal phase 3 SIERRA trial in patients with relapsed or refractory acute myeloid leukemia

Stockholm, February 23, 2023 - Immedica’s partner Actinium Pharmaceuticals Inc. has announced results for the primary and secondary endpoints from its pivotal phase 3 SIERRA trial of Iomab-B in patients aged 55 and above with relapsed or refractory acute myeloid leukemia (r/r AML) with active disease.

The SIERRA trial met its primary endpoint of superior durable Complete Remission (dCR = CR or CRp (CR with incomplete platelet recovery) lasting ≥6 months after initial CR/CRp following hematopoietic stem cell transplantation HSCT) with a high degree of statistical significance (p<0.0001). The median overall survival (OS) was 6.4 months for Iomab-B and 3.2 months for the physician´s choice of conventional care arm. More importantly, of the 13 patients (22 %) who achieved dCR on the Iomab-B arm 92% were still alive at 1 year and 60% at 2 years, and hence long-term survivors. Iomab-B enabled access to HSCT with 100% engraftment in all patients receiving a therapeutic dose of Iomab-B. Only 14 of the 77 patients randomized to the conventional care arm achieved a CR on physician’s choice of standard therapy and could proceed to HSCT. None of them had a CR duration of ≥6 months (dCR). Iomab-B was well tolerated compared to conventional care.

Results from the SIERRA trial were presented at the Tandem Meetings: Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR). The full abstract is found here: https://tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/22365.

In April 2022, Immedica and Actinium Pharmaceuticals, Inc. entered a license and supply agreement for Iomab-B, where Immedica has the commercial rights in Europe, the Middle East, and North Africa.

Anders Edvell, CEO of Immedica commented: “We are very encouraged by these results. Iomab-B has the potential to significantly improve the outcomes in a patient population that is underserved by current therapies. We look forward to continuing our collaboration with Actinium to make Iomab-B available for patients in our territories”.

SIERRA trial results

The SIERRA trial is a prospective, randomized, controlled phase 3 study comparing Iomab-B to physician’s choice of conventional therapy to patients ≥55 years of age with relapsed or refractory acute myeloid leukemia with active disease, a group of patients with dismal prognosis and few effective therapeutic options. Primary endpoint was the rate of dCR (≥ 6 months). Patients not achieving CR with conventional care could crossover (CO) to Iomab-B-based conditioning followed by HSCT. Forty patients from the conventional care arm actually crossed over. The outcome for CO patients receiving Iomab-B was similar to what was seen in the group randomized to Iomab-B.

SIERRA was conducted at 24 of the leading HSCT centers in the United States and Canada. SIERRA enrolled older, heavily pre-treated patients with active disease and high-risk characteristics who would not be offered HSCT in standard practice outside of a clinical trial and therefore have dismal survival outcomes of two to three months.

HSCT access and engraftment:

All patients (N=66) receiving the therapeutic dose of Iomab-B were able to access HSCT with 100% engraftment. Only 14 patients in the conventional care arm did eventually achieve a CR and could proceed to HSCT. The time from randomization to HSCT was more than doubled for these patients compared to patients transplanted after Iomab-B (median 29 vs. 66.5 days)

Primary endpoint – dCR:

• Iomab-B met the primary endpoint of dCR, i.e., a CR (or CRp) with a duration of at least 6 months following initial CR after HSCT, with a high degree of statistical significance (p<0.0001)
• 22% of patients (13/59) in the per protocol analysis achieved dCR in the Iomab-B arm compared to 0% of patients on the control arm.

Secondary endpoints – event free survival and overall survival:

• Iomab-B demonstrated significant improvement in EFS with a Hazard Ratio = 0.22, p<0.0001, which means Iomab-B reduced the probability of an event by 78%. Iomab-B numerically doubled the median overall OS compared to patients who were treated with conventional care without crossover (6.4 months vs 3.2 months).
• A high percentage of patients achieving dCR after Iomab-B are long term survivors: 92% and 60% were still alive 1 and 2 years after initial CR respectively.
• The median OS in the CO arm was 7.1 months.

Safety information:

• Iomab-B was well tolerated compared to conventional care.
• The incidence of sepsis was four times lower in the Iomab-B arm compared to patients undergoing HSCT in the control arm (6.1% vs 28.6%).

About Iomab-B
Iomab-B is an anti-CD-45 monoclonal antibody conjugated to the radioisotope ¹³¹I. CD45 is widely expressed on leukemia and immune cells including bone marrow progenitor stems cells. The radiation emitted from Iomab-B kills both the cells that the antibody binds to, and also the neighboring cells thereby delivering targeted radiation directly to leukemic cells and white blood cells in the myeloid tissue ablating the bone marrow while sparing healthy organs.

Iomab-B is a first-in-class targeted radiotherapy intended to improve patient access to potentially curative HSCT. Multiple studies have demonstrated increased survival in patients receiving HSCT, however, an overwhelming majority of patients with r/r AML do not receive HSCT as current approaches do not produce a remission, which is needed to advance to HSCT, or are too toxic.

Actinium intends to submit a Biologics License Application (BLA) seeking approval for Iomab-B in 2023 to address patients age 55+ with r/r AML with active disease. Iomab-B has been granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and has patent protection into 2037. Iomab-B has also been granted Orphan Drug Designation by the European Medicines Agency (EMA) and Immedica will now start to prepare marketing approval applications relevant for the European territory.

About Actinium Pharmaceuticals, Inc.
Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing targeted radiotherapies to deliver cancer-killing radiation with cellular level precision to treat patients with high unmet needs. Actinium's clinical pipeline is led by targeted radiotherapies that are being applied to targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a bone marrow transplant (HSCT), gene therapy or adoptive cell therapy, such as CAR-T, to enable engraftment of these transplanted cells with minimal toxicities. www.actiniumpharma.com

About Immedica Pharma
Immedica is pharmaceutical company, headquartered in Stockholm, Sweden, focused on the commercialization of medicines for rare and specialty diseases. Immedica’s capabilities cover marketing and sales, compliance, pharmacovigilance, quality assurance, regulatory and medical affairs as well as market access. Serving patients in more than 50 countries, Immedica is fully dedicated to helping those living with diseases which have a large unmet medical need.

Immedica’s therapeutic areas are within genetic & metabolic diseases, hematology & oncology and specialty care.

Immedica was founded in 2018 by the investment company Impilo and Buy-in-Management. Today Immedica employs more than 90 people across Europe and the Middle East.

For more information visit www.immedica.com

Immedica contact:

Linda Holmström

Head of Communication

linda.holmstrom@immedica.com

+ 46 708 73 40 95