Full Press Release Details
Dear Actinium Shareholder:
In 2020 thus far, we have made steady progress
with our Iomab-B SIERRA pivotal trial, which is in its final quartile of enrollment, and our Actimab-A combination trials in the
Relapsed and Refractory Acute Myeloid Leukemia (R/R AML) setting. We are on track and look forward to data updates related to this
progress by year-end; specifically, data from the first 75% of patients from the SIERRA trial, the Ad-Hoc interim analysis, and
POC data from our Actimab-A + CLAG-M combination trial. In addition, we have several other milestones across our platform that
will be reached in 4Q:2020 and 2021, setting the stage for a potentially transformational future for your company. We approach
these milestones with momentum across our clinical pipeline, enhanced R&D capabilities, a strong balance sheet and highly motivated
colleagues. We are excited for Actinium's future, grateful for your support and look forward to creating value for all stakeholders.
Attractive Multi-Product, Multi-Indication
Opportunity in R/R AML Emerges in 2020
The progress made this year with Iomab-B
and the Actimab-A therapeutic combination trials is exciting and potentially transformational. Taken together these programs can
address the still unmet needs of a large segment of patients with R/R AML and potentially change the way the disease is treated.
Despite 9 approved therapies for AML, a majority of patients relapse or become refractory at which point treatment options are
limited. Bone Marrow Transplant (BMT) remains the only curative treatment option but R/R AML patients typically cannot receive
one as they are unable to withstand the highly toxic chemotherapy conditioning agents currently being used. As depicted in the
graphic below, the ongoing pivotal Phase 3 SIERRA trial with Iomab-B is the backbone for our R/R AML strategy; enabling elderly,
unfit patients to access a BMT with the potential for improved survival. Our Actimab-A combination trials with CLAG-M and venetoclax
could be used either as therapeutics or a bridge to transplant in the fit and unfit patient segments. We eagerly await the data
events for Iomab-B and the proof of concept data for both Actimab-A combination trials by year-end and in 2021, respectively. Together
these results could set the stage for a much larger and attractive opportunity in R/R AML than either drug candidate alone.
Upcoming Data Could Set Stage for
Expanded Market Opportunity in R/R AML
The R/R AML patient population is largely
treated in approximately 75-100 tertiary care hospitals, which also conduct the majority of BMT procedures. Leveraging relationships
established with the leading AML treatment centers in our clinical trials and our supply chain capabilities, we believe that Iomab-B
and Actimab-A could be successfully commercialized into the tertiary care setting and envision building Actinium into a specialty
oncology company focused on addressing the R/R AML patient population with multiple products. Our programs are on the cusp of producing
data that can help us realize this vision.
2020 - Accomplishments Across
All Major Pipeline Initiatives
As we hear of COVID-19 ad nauseum,
I am proud to report that Actinium was able to accomplish many of its clinical goals despite clinical sites being severely hampered
for several months. Our SIERRA trial was able to maintain enrollment because the trial investigators needed to keep treating very
sick R/R AML patients and recognized the demonstrated benefit of Iomab-B from the 50 percent interim analysis. Throughout this
period, dedicated teams at Actinium and our clinical sites were able to ensure that our supply chain capabilities were fully operational.
Highlighted below are some of the achievements we have made in 2020 and outlook into our major programs.
Targeted Conditioning Pipeline -
Value Creating Data Events Within Reach
Iomab-B Program for BMT - Pivotal Phase
We note that, despite the late trial stage,
investigator interest driven by data updates published at the 50 percent mark has led to several additional sites joining or expected
to join the study. This data reported at the Transplantation & Cellular Therapy Conference showed that 100% of patients receiving
Iomab-B underwent a BMT and engrafted, the first sign of a successful BMT outcome. Only 18% of control arm patients successfully
received a BMT. Additionally, the difference in number of patients potentially evaluable for the primary endpoint, measured by
100-day non-relapse transplant related mortality, has remained consistent at roughly 6x greater for the study arm at the 25% and
50% enrollment updates. With the trial in its final quartile of enrollment, we look forward to data updates from the 75 percent
enrollment mark and the interim ad-hoc analysis by year-end. The strong investigator interest in Iomab-B is a barometer for the
unmet need and we are hopeful that Iomab-B will be able to provide these patients improved access to a BMT and better outcomes.
Iomab-ACT Program for CAR-T -
Proof of Concept Trial with MSK
We are collaborating with Memorial Sloan
Kettering Cancer Center (MSK) via an approach validating NIH STTR fast track grant to explore the benefit of using Iomab-ACT, a
low dose version of the ARC used in the Iomab-B program, to condition patients before they receive CAR-T therapy. MSK is a leader
in the field of cellular therapy and this trial is unique as it will be the first time an ARC has been used for conditioning for
any cellular therapy. The CAR-T construct, 19-28z, used in this trial, has proven efficacy in various blood cancers but is not
truly viable due to relatively high rates of cytokine release syndrome and neurotoxicity. Iomab-ACT can potentially address these
issues by selectively targeting and depleting immune cells implicated in these CAR-T toxicities and creating a better environment
for the CAR-T cells to expand and persist in order to attack the patient's cancer and potentially have lower side effects
and higher and more durable responses. We look forward to proof of concept data from this trial in 2021. There is an attractive
and potentially large opportunity for the Iomab-ACT program to become the universal conditioning regimen for CAR-T based therapies.
Other Conditioning Programs -
Actimab-MDS and Iomab-ACT for Gene Therapy
We have completed our interactions with
FDA and have a clear pathway to a pivotal trial after a short dose confirming Phase 1 study (which we believe will likely be 4uCi/kg
body weight) for the Actimab-MDS targeted conditioning study in high-risk patients with MDS or myelodysplastic syndrome. The start
of the gene therapy trial in HIV related lymphoma has been delayed as the University of California Davis was severely impacted
due to COVID-19 and cohort expansion in the trial which uses chemotherapy conditioning, highlighting the need improved conditioning
regimens. We will update on these programs as they move ahead in 2021.
CD33 Program Revitalization Via Therapeutic
Combination Trials Data
Our CD33 program is showing compelling
promise and could become an important driver of value. Recall, through the Phase 2 trial, we demonstrated that single-agent Actimab-A
was extremely potent (ORR of 69%) and had no extramedullary toxicity outside of myelosuppression. We are parlaying this profile
via a therapeutic combination strategy with established agents in R/R AML. As very few patients are cured with the 9 approved drugs,
R/R AML patients account for almost 70% of the AML population. Each of our Actimab-A combination trials adds low, sometimes sub-therapeutic
doses of Actimab-A, to established doses of drugs or drug cocktails and delivers internalized radiation to a highly radiation sensitive
liquid cancer. There is also a mechanistic synergy or potentiating effect possible from adding Actimab-A in the two combination
trials with CLAG-M and venetoclax. Actimab-A, in addition to its single agent activity can damage certain proteins like Mcl-1 and
act in concert with DNA damage response inhibitor drugs and yield extremely high patient response rates without compromising their
Supporting our approach are data from the
Actimab-A + CLAG-M trial which showed a very high remission rate of 86%, 60% higher than CLAG-M alone. This second dose cohort
combined a sub-therapeutic dose of Actimab-A with a standard CLAG-M regimen. Further, the minimal residual disease or MRD negative
rate was an impressive 71%, which bodes well for durability of response. Venetoclax combinations are arguably the most widely prescribed
regimen but most patients ultimately fail, and our trial is attracting significant investigator interest which has led to site
expansion. We are excited as we believe these data events can demonstrate the immense value creating potential of our CD33 program,
which has been largely overshadowed by Iomab-B and is deserving of further attention. We look forward to presenting updated POC
data from our CLAG-M combination and first human data from the venetoclax combination Phase 1 trial by year-end.
Why Bolster R&D Capabilities at
Actinium the company, was formed two decades
ago to harness the power of radioisotopes, in particular Actinium-225 or Ac-225, to treat and potentially even cure cancer. The
idea was far ahead of its time and the company certainly had its share of vicissitudes we are the sixth management team.
We restarted R&D three years ago, within a few months of our tenure, and have revitalized the aging patent portfolio, informed
CD45 and CD33 program expansion via our research and entered into a research partnership with a global biopharma company. We now
execute in a highly collaborative manner navigating complex scientific considerations, informed by commercial sensitivities, our
clinical know-how and supply chain expertise.
While no one has cured cancer, not even
with a radiotherapeutic since Actinium was formed, there have been certain high-profile successes with radiopharmaceuticals that
have created tremendous value for shareholders. This success has attracted new entrants and significant investments. Given a fortified