On January 12, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, reported that data from its pivotal Phase 3 SIERRA trial of Iomab-B have been accepted as a late-breaker presentation at the Transplantation & Cellular Therapy (TCT) Tandem Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR) (Press release, Actinium Pharmaceuticals, JAN 12, 2023, View Source;cellular-therapy-tandem-meetings-301720055.html [SID1234626225]). TCT, the largest bone marrow transplant (BMT) focused medical conference globally, is being held February 15 – 19, 2023 at the World Center Marriott in Orlando, Florida.

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TCT Late-Breaker Presentation Details:

Presentation Title: Efficacy and Safety Results of the SIERRA Trial: A Multicenter, Pivotal Phase 3 Study of Iomab-B Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Older Patients with Active, Relapsed or Refractory Acute Myeloid Leukemia

Date: Saturday, February 18, 2022

Time: 5:00 PM EST

Presenter: Dr. Boglarka Gyurkocza, Memorial Sloan Kettering Cancer Center

Location: World Center Marriot, Cypress 3

Actinium will host a conference call and webcast on Saturday, February 18, 2023 at 6:00 PM EST following the SIERRA late-breaker presentation at TCT. Additionally, Actinium will host a webcasted KOL event at 8:00 AM EST on Tuesday, February 28, 2023. Additional details will be announced in advance of these events and when available, they can be found on Actinium’s investor relations page View Source

About Iomab-B and the Pivotal Phase 3 SIERRA Trial
Iomab-B is a first-in-class targeted radiotherapy intended to improve patient access to potentially curative BMT by simultaneously and rapidly depleting blood cancer, immune and bone marrow stem cells that uniquely express CD45. Multiple studies have demonstrated increased survival in patients receiving BMT, however, an overwhelming majority of patients with blood cancers do not receive BMT as current approaches do not produce a remission, which is needed to advance to BMT, or are too toxic. Studied in over 400 patients, prior studies with Iomab-B have demonstrated nearly universal access to BMT, increased survival and tolerability in multiple clinical trials including the recently completed pivotal Phase 3 SIERRA trial in patients with active (leukemic blasts >5%), relapsed or refractory acute myeloid leukemia (r/r AML) age 55 and above. The SIERRA trial produced positive topline results, meeting its primary endpoint of durable Complete Remission (dCR) of 6 months with statistical significance (p<0.0001). Actinium intends to submit a Biologics License Application (BLA) seeking approval for Iomab-B to address patients age 55+ with r/r AML who cannot access BMT with currently available therapies. Iomab-B has been granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and has patent protection into 2037.

The pivotal Phase 3 SIERRA (Study of Iomab-B in Elderly relapsed or refractory AML) is a 153-patient, randomized, multi-center clinical trial, studying Iomab-B compared to the control arm of physician’s choice of salvage therapy. Control arm options included chemotherapies like cytarabine and daunorubicin and targeted agents such as a Bcl-2 inhibitor (Venetoclax), FLT3 inhibitors and IDH 1/2 inhibitors. The SIERRA control arm reflects real-world treatment of r/r AML patients with over 20 single agents or combination of agents as no standard of care exists for this patient population. Data from full patient enrollment presented at the Transplantation & Cellular Therapy Tandem Meetings in April 2022 showed that 100% of patients receiving Iomab-B accessed BMT and engrafted without delay. Iomab-B was also shown to be well tolerated given its targeted nature, consistent with its previous clinical data. The SIERRA trial enrolled patients at 24 leading transplant centers in the United States and Canada that perform over 30% of AML BMTs.

Developed at the Fred Hutchinson Cancer Research Center, a pioneer in the field of BMT, Iomab-B is supported by data in six disease indications including leukemias, lymphomas and multiple myeloma, which afflict over 100,000 patients annually. Actinium intends to pursue additional indications for Iomab-B beyond AML. Actinium also intends to pursue international regulatory approvals independently and through partnerships. In April 2022, Actinium licensed the European, Middle East and North African commercial rights for Iomab-B to Immedica AB, a fully-fledged independent pharmaceutical company headquartered in Sweden. In exchange, Actinium received an upfront payment of $35 million USD with the potential for an additional $417 million USD in regulatory and sales milestones and mid-twenty percent royalties. Europe represents a commercial opportunity double the size of the United States by number of patients with AML receiving BMT. Iomab-B has been granted Orphan Drug Designation by the European Medicines Agency (EMA) and has received positive Scientific Advice from the Committee for Medicinal Products for Human Use (CHMP) of the EMA indicating that the Phase 3 SIERRA trial design, primary endpoint and planned statistical analysis are acceptable as the basis for a Marketing Authorization Application.

On January 12, 2023 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported an investigator-initiated Phase 1b/2 trial evaluating the Company’s novel anthracycline, Berubicin, which will be conducted at the Pomeranian Medical University (PUM) in Szczecin, Poland (Press release, CNS Pharmaceuticals, JAN 12, 2023, prnewswire.com/news-releases/cns-pharmaceuticals-announces-investigator-initiated-phase-1b2-trial-to-be-conducted-at-the-pomeranian-medical-university-in-poland-301719938.html [SID1234626224]).

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The study, titled "Evaluation of the safety and efficacy of Berubicin in the treatment of central nervous system lymphomas," will be a single center, single-arm, open-label Phase 1b/2 clinical trial assessing the efficacy, safety, and pharmacokinetics of Berubicin in a multidrug treatment regimen for adult patients with newly diagnosed or relapsed/refractory primary central nervous system lymphoma (PCNSL) and non-Hodgkin’s lymphoma with central nervous system involvement (NHL-CNSI). The primary efficacy endpoint for the study is to evaluate the safety and tolerability of Berubicin in combination with other cytostatic agents and to determine the recommended Phase 2 dose (RP2D) of Berubicin.

"Based on the data seen to date, Berubicin has continued to demonstrate an overall safety profile more favorable than other known anthracyclines and we remain encouraged by its potential. We are committed to Berubicin’s continued development as a much-needed oncology tool and are therefore providing the study drug to the PUM for their Phase 1b/2 clinical study. Given the unmet needs and current prognosis for CNS lymphomas, the optimal treatment strategy is to improve overall survival, to which we believe Berubicin can contribute. We look forward to further understanding the potential of Berubicin in this disease and the findings from this study," commented John Climaco, CEO of CNS Pharmaceuticals.

Patients enrolled in the investigator-initiated Phase 1b/2 study will receive Berubicin in escalated doses in an accelerated model assigning one patient per cohort, which will reduce the number of patients that may be treated with sub-therapeutic doses. The purpose of the dose escalation strategy is to evaluate dose limiting toxicities (DLT) and establish the appropriate dose to utilize into Phase 2 (recommended Phase 2 dose, RP2D). The initial escalation by 40% in the next cohorts will be based on safety assessments. After completing a treatment cycle, if a patient does not have any DLTs, they can proceed to the next dose level, and additional patients can be enrolled to explore higher doses. If any patient experiences DLT, that dosing cohort will be expanded to 3 patients. If 2 patients develop DLT, the given dose will be considered toxic and the next cohort will start treatment at a dose reduced by 20%.

After considering the data from the Phase 1 clinical trial in patients with CNS gliomas, treatment of patients with CNS lymphomas is planned to start with a higher initial dose of Berubicin (4.8 mg/m2).

A total of up to approximately 60 patients are planned to be enrolled. The minimum participation in the study for an individual patient is approximately 21 weeks. After the end-of-treatment follow-up visit, patients will enter a post-study follow-up period of up to 3 years.

Berubicin is currently being evaluated for efficacy and safety in the treatment of glioblastoma multiforme (GBM), an aggressive and incurable form of brain cancer, by CNS Pharmaceuticals in an ongoing, potentially pivotal global study. For more information about the potentially pivotal Berubicin trial, visit clinicaltrials.gov and reference identifier NCT04762069.

About Berubicin
Berubicin is an anthracycline, a class of anticancer agents that are among the most powerful chemotherapy drugs and effective against more types of cancer than any other class of chemotherapeutic agents. Anthracyclines are designed to utilize natural processes to induce deoxyribonucleic acid (DNA) damage in targeted cancer cells by interfering with the action of topoisomerase II, a critical enzyme enabling cell proliferation. Berubicin treatment of brain cancer patients appeared to demonstrate positive responses that include one durable complete response in a Phase 1 human clinical trial conducted by Reata Pharmaceuticals, Inc. Berubicin, was developed by Dr. Waldemar Priebe, Professor of Medicinal Chemistry at The University of Texas MD Anderson Cancer Center.

On January 12, 2023 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ: MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported that the Phase 2 clinical trial evaluating MN-166 (ibudilast) in recurrent and newly diagnosed glioblastoma conducted at Dana-Farber Cancer Institute has completed enrollment (Press release, MediciNova, JAN 12, 2023, View Source [SID1234626223]). This Phase 1/2 clinical trial was divided into a dose-escalation phase (Part 1) followed by a fixed-dose phase (Part 2). Part 1 evaluated the safety and tolerability of an escalating dose of MN-166 (ibudilast) when given in combination with temozolomide (TMZ) and determined a safe and tolerable dose of MN-166 (ibudilast) to be used in Part 2 of the study. Part 2 will evaluate the efficacy of MN-166 (ibudilast) and TMZ combination treatment. Tumor tissues were obtained from the initial surgery or biopsy. We evaluated the correlation of MN-166 and TMZ combination therapy to clinical outcomes and tumor tissue analysis findings.

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Preliminary tumor tissue analysis and clinical outcome findings from Part 1 participants will be presented at the 20th Annual World Congress of SBMT (Society for Brain Mapping and Therapeutics) to be held February 16 – 19, 2023.

Kazuko Matsuda, MD, PhD, MPH, Chief Medical Officer of MediciNova, Inc., commented, "We have completed enrollment and are actively treating the remaining patients in Part 2 of the trial. We look forward to reporting the interesting findings from tumor tissue analysis and clinical outcomes at the 20th Annual World Congress of SBMT, including potential predictors of treatment response to MN-166 plus TMZ combination therapy in glioblastoma. We will release more information after SBMT meeting."

About Glioblastoma

According to the American Association of Neurological Surgeons, glioblastoma is an aggressive brain cancer that often results in death during the first 15 months after diagnosis. Glioblastoma develops from glial cells (astrocytes and oligodendrocytes), grows rapidly, and commonly spreads into nearby brain tissue. Glioblastoma is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that glioblastoma represents about 15% of all primary brain tumors and approximately 10,000 cases of glioblastoma are diagnosed each year in the U.S. Despite decades of advancements in neuroimaging, neurosurgery, chemotherapy and radiation therapy, only modest improvements have been achieved and the prognosis has not improved for individuals diagnosed with glioblastoma. Median survival is about 11-15 months for adults with more aggressive glioblastoma (IDH-wildtype) who receive standard treatment of surgery, temozolomide, and radiation therapy.

About MN-166 (ibudilast)

MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and is also in development for glioblastoma, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) was evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS).

As previously reported on Current Reports on Forms 8-K filed July 6, 2022, August 2, 2022 and August 9, 2022, on June 30, 2022, Ensysce Biosciences, Inc. ("Ensysce" or the "Company") entered into a Securities Purchase Agreement (the "SPA") for an aggregate financing of $8.0 million with institutional investors (Filling, Ensysce Biosciences, JAN 12, 2023, View Source [SID1234626219]). At two closings under the SPA, which occurred on June 30, 2022 and August 8, 2022, the Company issued to the investors (i) senior secured convertible promissory notes in the aggregate principal amount of $8.48 million for an aggregate purchase price of $8.0 million (the "Notes") and (ii) warrants (the "Warrants") to purchase 9,335,780 shares of the Company’s common stock, par value $0.0001 per share (the "Common Stock") in the aggregate. Under the SPA, the conversion price for converting Notes into the Common Stock, after several downward resets, is $2.006 per share (the "Conversion Price"), subject to adjustment under certain events. In addition, following a reverse stock split in October 2022, the number of Warrants is now 466,788.

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On January 12, 2023, the parties to the SPA agreed to a Letter Agreement amending the SPA ("Letter Agreement") to take certain actions. Among other matters, the parties to the Letter Agreement (i) reduced the Conversion Price for the remaining balance of the Company’s outstanding Notes from $2.006 to $0.7512 (the "New Conversion Price") for the period from January 12, 2023 until May 12, 2023 (the "Period"), and (ii) agreed to register any additional shares of Common Stock required to give the holders registered shares upon conversion of the Notes if exceeding those shares already registered on a Form S-3 that was declared effective on December 29, 2022. The remaining balance of the Notes was $3,339,931 as of the date of the Letter Agreement. Following the Period, the prior conversion price of $2.006 will apply. In addition, the parties have agreed that to the extent the investors receive shares as an interest payment or upon a redemption notice pursuant to Sections 2(a) and 6(b) of the Notes, any cash true-up payment based on the New Conversion Price will not be required to be paid for one hundred and twenty days. The parties have also agreed that accelerations of payment that are permitted under the Notes for any given month may be made over four conversion notices instead of two conversion notices during the period from January 12, 2023 until May 12, 2023.

The New Conversion Price meets a minimum price requirement established by The Nasdaq Stock Market in connection with a potential issuance of 20% or more of the Common Stock of a public company or 20% or more of the voting power outstanding before the potential issuance. The Letter Agreement may result in the need for the Company to issue more than 20% of its shares of Common Stock. If the New Conversion Price did not meet the minimum price requirement, then the Letter Agreement would have to be approved by Company stockholders. The New Conversion Price is the price that was the lower of: (i) the Nasdaq Official Closing Price (as reflected on Nasdaq.com) immediately preceding the signing of the Letter Agreement; or (ii) the average Nasdaq Official Closing Price of the Common Stock (as reflected on Nasdaq.com) for the five trading days immediately preceding the signing of the Letter Agreement. On the date of execution of the Letter Agreement, the (i) the Nasdaq Official Closing Price (as reflected on Nasdaq.com) immediately preceding the signing of the Letter Agreement was $0.7600; and (ii) the average Nasdaq Official Closing Price of the Common Stock (as reflected on Nasdaq.com) for the five trading days immediately preceding the signing of the Letter Agreement was $0.7512.

There is no change to the exercise price of the Warrants because of the execution of the Letter Agreement. The Letter Agreement also includes certain conditions that the Company must satisfy in connection with the transaction.

The Company has registered with the Securities and Exchange Commission (the "SEC") the resale of the shares of Common Stock issuable upon conversion of the Notes as well as the shares of Common Stock issuable upon the exercise of the Warrants pursuant to the Registration Rights Agreement, dated June 30, 2022, by and among the Company and the purchasers signatory to the SPA. The Company registered the resale of additional shares of Common Stock upon conversion of the Notes in December 2022 and may be required to register additional shares of Common Stock upon conversion of the Notes as a result of the Letter Agreement.

On January 12, 2023 Spago Nanomedical reported Preclinical data with Spago Nanomedical’s radionuclide therapy concept Tumorad was recently published in the scientific journal ACS Omega (Press release, Spago Nanomedical, JAN 12, 2023, View Source [SID1234626209]). The paper describes the composition, stability and mode of action for the drug candidate 177Lu-SN201 and concludes that the candidate’s properties are suitable for systemic treatment of cancer. BioStock reached out to CEO Mats Hansen to learn more on what this means for the project.

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In recent years, research in radiation therapy for cancer has advanced and has led to several approved drugs, such as Novartis’ Luthatera which was given the green light by the EMA in 2017 and by the FDA in 2018. The interest in this type of treatment is significant and can be illustrated by Lutathera’s turnover, which in 2021 amounted to USD 475 million. Learn more.

With new targeted treatments, it is now possible to achieve very high precision in combination with the validated effect of radiation treatment. The next generation of radionuclide treatments includes Spago Nanomedical‘s candidate 177Lu-SN201. The candidate is part of the company’s Tumorad project, which is currently being prepared for an upcoming phase I/IIa study.

Positive preclinical results published

Recently, Spago Nanomedical published preclinical data regarding 177Lu-SN201 in the scientific journal ACS Omega.In the peer-reviewed article, the authorsdescribethecandidate’s composition, stability andmode of action.

In short, the results show that the drug candidate accumulates in cancerous tumours and inhibits their growth, which leads to prolonged survival in a preclinical model for colon cancer.

The preclinical results indicate that the candidate is well suited for systemic treatment of cancer.

Comments from the CEO
BioStock reached out to Spago Nanomedical’s CEO Mats Hansen to learn more about the published results and what they mean for the company.

Mats, radionuclide therapies have attracted a lot of interest lately, why is that?

Mats Hansen, CEO Spago Nanomedical

– Radiation therapy has been a cornerstone of cancer treatment for a long time. The possibilities of achieving endogenous radiation treatment were previously limited to specific cancers such as thyroid cancer and bone cancer.

– When Algeta’s Xofigo was approved about ten years ago, a new generation of targeted radionuclide therapies emerged. A major breakthrough came 5-6 years ago with Novartis’ Lutathera, a drug that has an annual turnover of almost USD 500 million in a specific group of patients with so-called neuroendocrine tumours.

– With today’s radionuclide therapies, the effectiveness of radiation treatment can be combined with high-precision targeting of tumours. This means that we can now treat tumours with radiation that was previously not possible to access. So far, however, the field is limited to a few tumour types which it is possible to target biologically.

– In this context, Tumorad could potentially further contribute to the area through its mechanism based on physiological targeting, which means that significantly more types of tumours could be treated.

What was the purpose of the preclinical studies, the results of which are now published?

– The results that have now been published in a peer-reviewed scientific journal provide an overall picture of the composition and mode of action of our drug candidate 177Lu-SN201.

– As the article describes how the nanoparticle’s chemical design provides a strong and sustainable binding of radioisotope, a favourable distribution in the body, as well as a good inhibiting effect on tumour growth and prolonged survival, it marks an end to the preclinical development phase and lays the foundation for further development in clinical studies.

In your press release, you mention that your candidate accumulates to a greater extent in tumours than Lutathera does – what does that mean for the project?

– The radioactive isotope in Lutathera, 177lutetium, is the same as we use in Tumorad. The fact that we can preclinically show that our candidate with the injected dose accumulates in at least as good a way as Lutathera gives a very significant indication of the possibilities of being able to treat cancer patients.

– As I mentioned earlier, Tumorad’s targeting is not dependent on binding to a specific protein that is expressed on the cancer cell you want to access, but that it accumulates physiologically in the tumour tissue via the EPR effect (Enhanced Permeability and Retention effect).

– This means that Tumorad can potentially be used as monotherapy or combination therapy in several cancers, even those that cannot be treated effectively today.

What are the implications from preclinical results for the preparation of the upcoming clinical study with Tumorad?

– These results, together with the favourable results from the regulatory toxicology studies we have conducted, strengthen the basis for our application to enter the clinic.

Finally, what is the current status of the Tumorad programme?

– Preparations for the phase I/IIa study are in full swing, for example, GMP manufacturing of the candidate is progressing according to plan, and we aim to submit an application for clinical trial shortly.