Will Actinium Be Big Pharma’s Next Radiopharmaceuticals Acquisition?

It has felt lately that there may be not be enough radiopharmaceutical companies to satisfy big pharma’s appetite. First, in December 2023, Eli Lilly and Company purchased POINT Biopharma Global Inc. with its lutetium-based portfolio for $1.4bn. That same month, Bristol Myers Squibb Company purchased RayzeBio, Inc., including its Phase III actinium-based RYZ101, for $4.1bn. Then in March, AstraZeneca PLC bought Canadian biotech Fusion Pharmaceuticals Inc. for $2bn. And on 2 May, Novartis AG acquired Mariana Oncology, a purchase the big pharma said will enhance its research capabilities and clinical supply capacity in radioligand therapies.

The question is begged: who’s next?

In a 2 May 2024 note, a H.C. Wainwright analyst singled out Actinium Pharmaceuticals, Inc. as having “the pipelines, resources and expertise” to make it a suitable candidate for big pharma’s picking. So, what does Actinium have to offer?

Platform

New York-based Actinium’s Antibody Warhead Enabling (AWE) technology produces antibody-radiation conjugates (ARCs) that can precisely target radiation as well as administering synergistic pharmacological treatments using monoclonal antibodies. The platform has employed several radioisotopes, from beta-emitters like Iodine-131 (I-131) and Lutetium-177 (Lu-177) to the alpha-emitter Actinium-225 (Ac-225), depending on the needs of the indication.

The company is the most advanced biotech in employing Ac-225, which it notes is the most powerful medical grade radioisotope currently available. Its radiation is emitted within only several millimeters, making it suitable for radiotherapy.

Actinium has fully integrated R&D facilities in New York City and can manufacture Ac-225. The isotope is highly sought-after as it is used in clinical trials for a number of conditions and there is growing global demand for it. 

Pipeline

The company’s clinical pipeline focuses on pre-transplant conditioning and treatment for hematological cancers, most notably acute myelogenous leukemia, and conditioning assets for gene and cell therapies.

Actinium licensed its lead program, Iomab-B, from the Fred Hutchinson Cancer Research Center. The asset is a first-in-class targeted anti-CD45 radioimmunoconjugate that simultaneously depletes the cancer and eliminates CD45-expressing bone marrow stem cells, preparing patients for bone marrow transplantation. It is comprised of an anti-CD45 monoclonal antibody, apamistamab, linked with the radioisotope iodione-131, which has a longer pathlength that can reach into the niches of the bone marrow.

The treatment has been studied in over 400 patients, mostly relapsed/remitting AML patients. Such patients typically cannot access hematopoietic stem cell transplantation (HSCT) and account for roughly half of all AML patients.

In the 153-patient Phase III SIERRA study, all patients with r/r AML given Iomab-B were able to proceed to HSCT with 100% engraftment. In contrast, only 17% of those receiving the control standard of care were eligible for BMT. Forty of the control arm patients that switched to Iomab-B treatment after failing to qualify for HSCT and all subsequently underwent transplantation.

In addition to increasing the likelihood of transplantation, 22% of patients in the Iomab-B group had durable complete remission (dCR) six months after transplant, compared to 0% of control patients. Overall survival was 92% and 60% at one and two years, respectively, for those who achieved dCR in the Iomab-B group.

SIERRA findings also showed the drug was well-tolerated, with lower rates of sepsis, febrile neutropenia, mucositis and acute graft-versus-host disease, compared to control patients who underwent HSCT.

The company plans to submit a Biologic License Application in the United States and a Marketing License Application in the European Union this year for Iomab-B.

Actinium’s second most advanced asset, Actimab-A, is a CD33-targeting radiotherapeutic for patients with r/r AML. Actimab-A employs a mutation-agnostic mechanism and has potential to be used as combination backbone therapy in highly radiosensitive, mutation-rich AML patients.

A proof-of-concept trial of Actimab-A with CLAG-M, the standard therapy for r/r AML, included 23 patients, comprised of heavily pre-treated individuals and those with TP53-mutated disease. In that study, 64% of eligible patients proceeded to transplant, with a median 24-month survival among transplanted patients.

Other pipeline assets include Actimab-A with venetoclax for r/r AML, Iomab-ACT as gene and cell therapy conditioning, a planned combination of Actimab-A with venetoclax and HMA for r/r AML, and several undisclosed preclinical solid tumor programs.

Partnerships

Actinium has licensed the commercialization rights to Iomab-B for Middle East and North Africa to Immedica AB for $35m upfront and up to $417m more in potential regulatory and sales milestones as well as royalties.

Actinium has a long-standing collaboration with Astellas Pharma, Inc. on the development of “theranostics” to image, diagnose and treat solid tumors with Ac-225-based agents. The financial details are undisclosed.

Actinium also has research and strategic collaborations with Aveo Oncology and EpicentRx, Inc. to develop a novel Ac-225-based ARC targeting ErbB3 for solid tumors. Again, the financial details were undisclosed.

CEO On The Company’s Strengths

Sandesh Seth, who first joined Actinium on the board of directors while an investment banker and ultimately assumed the CEO role in 2017, noted that while blood cancers represent only 11% of overall cancer cases, they account for roughly 26% of cancer drug spending and four of the top 10 selling cancer drugs are for blood cancers.

“Blood cancer therapies have an outsized revenue share relative to the patient population,” he told In Vivo. “With large pharma building solid tumor radiopharmaceutical portfolios, we believe blood cancer radiotherapies represent a natural complement.”

With compelling data in hand and leadership in the hematology radiopharmaceuticals market, Seth noted the company also has strengths in manufacturing and supply chain capabilities that make it an attractive target for a big pharma takeout.

“We have developed a proprietary technology and method to manufacture Ac-225 in a cyclotron using Radium-226 as the starting material. We expect to be able to produce Ac-225 at commercial scale using our method resulting in significantly more Ac-225 available to treat patients at a cost of 10-20 times lower than currently available material,” he said. “For every 1,000 patients treated, this would equate to over $10m in savings.”

Additionally, Actinium developed “final mile” capabilities during the SIERRA trial, building mobile shielding technology that enabled Iomab-B to be administered in a normal hospital room with radiation exposure to caregivers that is a fraction of the occupational limit and “less exposure than you would get on a round-trip cross country airline flight,” he noted.

Actinium is also specialized in its use of monoclonal antibodies as ligands, unlike Novartis’s Pluvicto (lutetium Lu 177 vipivotide tetraxetan) and Lutathera (lutetium Lu 177 dotatate), which both use peptide ligand as the conjugates. Actinium’s antibody radiation conjugates (ARCs) are an “evolution of ADCs, with radioisotope payloads offering several advantages over the toxin payloads used in ADCs, such as not requiring internalization of the target or the need for high target expression.”

“Also, being a biologic drug, they have up to 12 years of market and data exclusivity and are less subject to generic competition,” Seth noted.