SNMMI 2023 Annual Meeting Abstract of the Year Awarded to Actinium’s Iomab-B Phase 3 SIERRA Data

On June 26, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM, ‘Actinium’), a leader in the development of targeted radiotherapies, reported that the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2023 Annual Meeting selected Abstract 685 titled "Individualized dosing for high-dose targeted radiation of hematopoietic cells with Iomab-B (I131-apamistamab) prior to HCT in relapsed/refractory acute myeloid leukemia (R/R AML): Safety and efficacy results from the pivotal phase 3 SIERRA trial" as the Abstract of the Year (Press release, Actinium Pharmaceuticals, JUN 26, 2023, View Source [SID1234632887]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"It is a great honor for this SIERRA data abstract and this team of esteemed abstract authors to have received this award highlighting Iomab-B’s potential for people with relapsed and refractory AML," said Sandesh Seth, Chairman and Chief Executive Officer. "Today’s SNMMI honor represents the fourth oral presentation of the SIERRA trial data at prestigious medical conferences in 2023, including TCT, EBMT, and EHA (Free EHA Whitepaper). The extensive global recognition of the SIERRA results highlights Iomab-B’s potential to transform outcomes for the significant number of people with relapsed or refractory AML by enabling increased access to bone marrow transplant via a targeted radiotherapeutic. We are committed to file our BLA submission with U.S. Food and Drug Administration in the second half of this year in our endeavor to bring this new radiotherapeutic to people with great need."

"Elderly patients with active, relapsed/refractory AML have a very poor prognosis and currently have very limited treatment options. In routine clinical practice, these patients are not being considered for potentially curative bone marrow transplant," said Neeta Pandit-Taskar, MD, lead abstract author, attending physician, Molecular Imaging and Therapy Service, in the Department of Radiology at Memorial Sloan Kettering Cancer Center, and professor at Weill Cornell Medical College, in New York, New York. "This pivotal study showed that a single personalized dose of Iomab-B enabled all patients who received the therapeutic dose to have access to potentially curative bone marrow transplant, compared to only 17 percent of patients who received conventional care. Iomab-B also demonstrated long-term survival benefit for patients who met the primary endpoint, and safety of the Iomab-B led regimen was excellent. In addition, the visibility and cross-functionality of nuclear medicine was clearly demonstrated, strengthening the collaborative effort between nuclear medicine, nursing, and transplant teams. This will add further growth and impetus to use of nuclear medicine in planning and administration of theranostic radioimmunotargeted therapy."

AML is one of the most lethal forms of leukemia in adults. The American Cancer Society estimates that 20,380 people will be diagnosed with AML and more than 11,300 will die from the disease in 2023. Patients with relapsed or refractory disease represent the largest segment of AML patients.

AB Science receives Notice of Allowance for European patent covering masitinib in the treatment of metastatic castrate refractory prostate cancer (mCRPC)

On June 26, 2023 AB Science SA (Euronext-FR0010557264-AB) reported that the European Patent Office has issued a Notice of Allowance for a patent relating to methods of treating (mCRPC) with its lead compound masitinib, based on findings from study AB12003 [1] (Press release, AB Science, JUN 26, 2023, https://www.ab-science.com/ab-science-receives-notice-of-allowance-for-european-patent-covering-masitinib-in-the-treatment-of-metastatic-castrate-refractory-prostate-cancer-mcrpc/ [SID1234632886]). This new European patent provides intellectual property protection for masitinib in the treatment of mCRPC until 2042.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Masitinib is positioned in combination with docetaxel as a treatment of mCRPC patients who are eligible to chemotherapy; that is to say, it is administered directly following the metastatic hormone-sensitive prostate cancer (mHSPC) treatment space.

Although there are numerous treatments in the mHSPC treatment space, there is currently no drug registered for use in combination with docetaxel in patients with mCRPC, despite docetaxel having been approvedalmost 20 years ago. Historically, there has been a high failure rate of trials studying combinations of docetaxel and new targeted agents, with study AB12003 being a rare example of a phase 3 clinical trial that showed improvement in progression-free survival (PFS) for masitinib in combination with docetaxel.

The Notice of Allowance (NOA) means that the European Patent Office intends to grant the patentapplication, EP4175639A1, after the completion of certain formal procedural steps. Once granted, the patent can be kept in force until May 2042. A European NOA is issued after an examiner determines that a patent application satisfies all requirements for patentability under the European Patent Convention.

More specifically, this patent provides protection of masitinib and related compounds for treatment of mCRPC in a patient subpopulation with low metastatic involvement (as measured by baseline alkaline phosphatase levels). This patient population is fully consistent with results from masitinib study AB12003 [1] and the on-going clinical development program of masitinib in mCRPC. As a reminder, key results from study AB12003 include:

Masitinib (6.0 mg/kg/day) plus docetaxel conferred a significant progression-free survival (PFS) benefit in mCRPC patients with baseline alkaline phosphatase levels (ALP) less than or equal to 250 IU/L; hazard ratio of 0.79 [0.64,0.97] (p=0.0087), corresponding to a 21% reduction in risk of progression relative to control.

Assessment of PFS rates was convergent with this primary outcome, with 12, 18, and 24-month PFS rates showing significant improvement in favor of masitinib plus docetaxel relative to control: 1.6-fold (p=0.0035), 1.9-fold (p=0.0001) and 1.9-fold (p=0.0028), respectively.

A progressively greater masitinib treatment effect was observed for lower baseline ALP levels (i.e., less advanced metastatic disease), with a significant 47% reduced risk of progression in patients with ALP less than or equal to 100 IU/L (hazard ratio=0.53, p=0.002).

The masitinib plus docetaxel safety profile was acceptable, consistent with the known masitinib profile and with no new safety signals observed.

Although localized disease is associated with high survival rates, metastatic prostate cancer still represents an unmet medical need with a 5-years survival rate of about 32%.

References

[1] Pavic, Michel; Hermine, Olivier; Spaeth, Dominique LBA02-11 Masitinib plus docetaxel as first-line treatment of metastatic castrate refractory prostate cancer: results from study AB12003, Journal of Urology: September 2021-Volume 206-Issue Supplement 3. doi: 10.1097/JU.0000000000002149.11

[2] American Cancer Society. Cancer Facts & Figures 2023. Atlanta: American Cancer Society; 2023. Accessed June 2023. View Source

About study AB12003 Study

AB12003 was a prospective, placebo controlled, double blind, randomized, phase 3 trial, evaluating masitinib (6.0 mg/kg/d) in combination with docetaxel (IV 75 mg/m² plus prednisone for up to 10 cycles) as a first-line treatment of metastatic castrate resistant prostate cancer (mCRPC). Eligible patients were chemo-naïve with confirmed mCRCP, who had progressed on previous abiraterone treatment or were indicated for docetaxel treatment, and had a ECOG ≤1. Primary analysis was performed on a pre-specified targeted subgroup, defined as patients with baseline alkaline phosphatase levels (ALP) ≤250 IU/L, and on the overall population. Primary endpoint was progression free survival (PFS) (PCWG2 definition). The study was successful if improvement in median PFS relative to control reached a 3.9% level of significance for the target subgroup (alpha split with fallback procedure to conserve overall type-I error at 5% for the overall study cohort). Primary analysis was based on 450 patients in the targeted subgroup (ALP ≤ 250 IU/L). There was a total of 712 patients in the overall study cohort.

About masitinib

Masitinib is a orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can bedeveloped in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and microglia and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases.

Innovent and RemeGen Enter into Clinical Trial Collaboration Investigating Combination Therapy of TYVYT® (sintilimab injection) and Novel ADC Candidates for Advanced Solid Tumors in China

On June 25, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and RemeGen Co., Ltd. (688331.SH/09995.HK), reported that they entered into a clinical trial collaboration and supply agreement with for the combination therapies of TYVYT (sintilimab injection) with RC88, a novel mesothelin(MSLN)-targeting antibody-drug conjugate (ADC), or RC108, a novel c-Met-targeting ADC, respectively, as potential treatment options for advanced solid tumors in China (Press release, Innovent Biologics, JUN 25, 2023, View Source [SID1234632879]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the agreement, Innovent will provide clinical drug supplies of TYVYT (sintilimab injection) during the clinical trial collaboration. RemeGen will conduct Phase 1/2a clinical studies to evaluate the anti-tumor activity and safety of the combination therapy of TYVYT (sintilimab injection) with RC88 or RC108 in Chinese patients with advanced solid tumors.

TYVYT (sintilimab injection) is an innovative PD-1 inhibitor co-developed by Innovent and Eli Lilly and Company. In China, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. TYVYT (sintilimab injection) is the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types in the NRDL – including non-squamous NSCLC, squamous NSCLC, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer, as well as the first and the only immunotherapy medicine for gastric cancer in the NRDL.

RC88 is a novel MSLN-targeting ADC independently developed by RemeGen. RC88 is currently being investigated in an ongoing Phase 1 clinical trial, which was approved by the NMPA in November 2018. The preliminary results demonstrated anti-tumor activity and a manageable safety profile of RC88 monotherapy in MSLN-positive advanced solid tumors. Preclinical studies also showed that RC88 can selectively delivers a potent cytotoxic payload to MSLN-expressing cells through internalization, thus inducing G2/M arrest and apoptosis. When combined with PD-1/PD-L1 or other immune checkpoint inhibitors (ICIs), RC88 can induce immunogenic cell death (ICD), releasing a series of signaling molecules to further activate T cells, enhance tumor immune response, and synergistically exert a stronger anti-tumor effect.

RC108 is a novel c-Met targeting ADC independently developed by RemeGen. RC108 is currently being investigated in an ongoing Phase 1 clinical trial, which was approved by the NMPA in November 2020. The preliminary results demonstrated anti-tumor activity and a manageable safety profile of RC108 monotherapy in c-Met-positive advanced solid tumors. Preclinical studies also showed that RC108 can induce tumor-specific adaptive immunity and increase the infiltration of T cells into the tumor microenvironment, while anti-PD-1 monoclonal antibody can activate T cells to enhance anti-tumor killing effect. Therefore, it is expected that the combination therapy of RC108 and sintilimab can not only improve antigen presenting by dendritic cells , but also boost the tumor killing of T cells, therefore bringing in synergistic tumor inhibition effect.

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to collaborate with RemeGen to further explore the combination therapy potential of sintilimab injection and novel ADC candidates. Preclinical studies has suggested the synergistic anti-tumor effects, which supports the investigation of combining ADCs with an anti-PD-1 monoclonal antibody to improve patient outcomes and overcome drug-resistance. As immunotherapy advanced into next era of development, we hope to strengthen the leading position of sintilimab as a backbone immunotherapy as well as investigate the new opportunities of combination therapies, and provide better treatment options for more cancer patients. "

Ms. Na Su, Senior Vice President of RemeGen, stated "Collaborating with Innovent is an important advancement in the research and commercialization strategy for the combination therapy of RC88 and RC108. The combination of RC88 and RC108 with sintilimab provides an innovative treatment approach that targets two different targets simultaneously. The mechanisms are complementary and synergistic, helping to overcome or delay resistance, achieve multi-pathway targeting of tumors, and provide an efficient solution for unmet clinical needs."

About RC88 ADC

RC88 is a novel anti-mesothelin ADC developed by RemeGen, which is formed by a recombinant humanized anti-MSLN monoclonal antibody conjugated to the microtubule inhibitor MMAE via a Linker. It includes an MSLN antibody moiety (also known as RC88 naked antibody), a linker, and a small molecule moiety of the cytotoxic pentapeptide MMAE. RC88 binds hMSLN with high affinity and specificity and can compete with endogenous ligands. It can kill tumor cells with different expression levels of MSLN, and the killing effect is positively correlated with the expression of MSLN. Functional studies on the Fc fragment showed that the Fc-mediated effect was not a major role in the effect of this drug. Based on promising preclinical data, a phase 1 study has been moving forward quickly.

About RC108 ADC

RC108 is a targeted antibody-drug conjugate (ADC) developed by RemeGen for the treatment of solid tumors with positive expression of the cell-matrix epithelial transition factor (c-MET). RC108 consists of a c-MET targeting antibody, a linker, and a small molecule cytotoxin. Its mechanism of action is similar to RC48, as it can selectively bind to c-MET-positive tumor cells, mediate antibody internalization, and effectively deliver the cytotoxin to cancer cells, achieving a good tumor-killing effect. In November 2020, RemeGen received approval from the National Medical Products Administration to conduct Phase 1 clinical trials of RC108 targeting c-MET-positive advanced solid tumors in China. The trial is currently progressing smoothly, and preliminary results show that RC108 has anti-tumor activity against c-MET-expressing solid tumors and is well-tolerated. In December 2022, RC108 obtained clinical trial permission from the U.S. Food and Drug Administration (FDA) to conduct clinical research in patients with c-MET-positive solid tumors. In April 2023, a combination therapy involving RC108 was approved to conduct Phase 1b/2 clinical research in China, targeting patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations who have failed treatment with MET expression of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Preclinical study results showed that RC108 induces tumor-specific adaptive immunity, increases T-cell infiltration into the tumor microenvironment, and PD-1 monoclonal antibodies activate T-cells, enhancing anti-tumor immune responses. Therefore, it is expected that the combination of RC108 and PD-1 antibodies can enhance dendritic cell presentation of tumor antigens and strengthen T-cell killing of tumor cells, resulting in an enhanced synergistic anti-tumor effect.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells[i]. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. The updated NRDL reimbursement scope of TYVYT (sintilimab injection) include:

For the treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
For the treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy.
Additionally, sintilimab has been approved in combination with bevacizumab and chemotherapy (pemetrexed and cisplatin) for the treatment of patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy.

Besides, two clinical studies of sintilimab have met their primary endpoints:

Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

NEXI, first-in-class immunotherapy drug, IND ‘acceleration pedal’ next year

On June 23, 2023 Nexi, reported that its ‘first-in-class’ drug with its platform technology and antibodies to discover factors that cause refractoriness to existing cancer immunotherapy drugs, is accelerating with the goal of submitting a clinical trial plan (IND) in the first half of next year (Press release, NEX-I, JUN 23, 2023, View Source;mode=VIEW&num=44&category=&findType=&findWord=&sort1=&sort2=&page=1 [SID1234643438]). The company is preparing to emerge as a dark horse in the domestic bio industry with a two-track strategy that also looks at the possibility of technology transfer, including collaboration with global pharmaceutical companies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Kyung-wan Yoon, CEO of NEXI, said, "During the last BioUSA period, we continued discussions with a number of global pharmaceutical companies focusing on preclinical data of cancer immunotherapy drugs currently under development. As the preclinical data is positive and we are targeting a completely new target with First in Class. "I’m looking forward to the next process," he said.

NexI is developing innovative new drugs that can treat incurable cancers that do not respond to immunotherapy. We developed a platform to identify the mechanisms that cause refractoriness to anti-cancer immunotherapy and discover the causative factors of refractoriness. In addition, innovative immunotherapy drugs ‘NXI-101’ and ‘NXI- 201’ is being developed.

Non-small cell lung cancer was given priority and more than 20 types of immunotherapy-refractory cancer models, including colon cancer and cervical cancer, were constructed.

Nexi was founded in 2021 by CEO Yoon, who served as Genome & Company’s vice president (CSO). Although it is a new company, it has a large number of professional researchers who have been studying cancer immunotherapy and refractoriness for more than 20 years, and is attracting attention from the industry by producing remarkable results one after another in a short period of time. Daewoong Pharmaceutical participated in the Pre-A Series investment, and Green Cross later participated in the Series A investment, attracting an investment worth 22 billion won last year, a cold period for bio investment.

CEO Yoon said, "We are developing our core pipeline, NXI-101, with the goal of applying for IND and administering the first patient in April next year," and added, "We will increase the likelihood of success in technology commercialization in the global market."

Jubilant Radiopharma and Evergreen Theragnostics Announce Collaboration for the Sale and Distribution of Neuroendocrine Tumor Diagnostic OCTEVY™, (Kit for Preparation of Ga 68 DOTATOC Injection), pending FDA approval in 2H 2023

On June 23, 2023 Jubilant Draximage Inc. (dba, Jubilant Radiopharma), a Jubilant Pharma Company, through it’s Radiopharmacy business division which maintains the second largest nuclear medicine pharmacy network in the US, and Evergreen Theragnostics, Inc., a radiopharmaceutical company focused on improving the available options for cancer patients, reported a new agreement for Jubilant’s radiopharmacy business to prepare, sell, and distribute doses of OCTEVY (Kit for Preparation of Ga 68 DOTATOC Injection) to positron emission tomography (PET) customers across the US (Press release, Jubilant Radiopharma, JUN 23, 2023, View Source [SID1234632878]). OCTEVYTM is pending approval by the United States Food & Drug Administration (FDA), which is expected in 2H 2023.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

OCTEVY is currently under evaluation by the FDA as a potential radioactive diagnostic agent indicated for use with PET for the localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients. If approved, OCTEVY can provide a new imaging option for healthcare providers to aid in the management of NETs in their patients.

Under the terms of the agreement, upon regulatory approval, Jubilant will reconstitute, radiolabel, and deliver OCTEVY doses ordered by hospitals and independent PET imaging centers in the United States.

About Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are a diverse set of cancers that originate in neuroendocrine cells, which are cells that carry messages from the nervous system to the endocrine system. Because neuroendocrine cells are located in many organs, NETs are often heterogeneous in their symptoms and therefore difficult to diagnose. The incidence of NETs are low, but are increasing, likely in part due to increased diagnosis of the disease. Once a patient has been identified as having a NET, they will often undergo a PET scan to localize and state the cancer, which will help the care team identify the best course of treatment.

About OCTEVY

OCTEVY (Kit for Preparation of Ga 68 DOTATOC Injection), is currently under evaluation by FDA as a radioactive diagnostic agent indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients. OCTEVY is supplied as a 2-vial kit to radiopharmacies which allows for direct preparation of Ga 68 DOTATOC injection with the eluate of Gallium from an on-site generator at the radiopharmacy. OCTEVY is not currently approved by the FDA and is not yet available for sale in the United States.