Numab and 3SBio’s Sunshine Guojian Expand Partnership to Develop Novel T Cell Engager NM28

On December 14, 2021 Numab Therapeutics AG (Numab) and 3SBio Inc. ("3SBio", HKEX:1530) reported that 3SBio’s subsidiary Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd. ("Sunshine Guojian") exercised its option for an exclusive regional license for the development and commercialization of NM28, a potential best-in-class bivalent mesothelin (MSLN)-targeting CD3 T cell engager (Press release, Numab, DEC 14, 2021, View Source [SID1234597111]).

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Under the terms of this collaboration, which builds on the existing relationship between the two parties established in 2019, Sunshine Guojian will have exclusive rights to develop and commercialize NM28 in the Greater China area, including mainland China, Hong Kong, Macao and Taiwan. Numab retains NM28 rights for the rest of the world.

"We are very pleased to enter into this agreement with Sunshine Guojian, which illustrates our global development strategy to form regional partnerships in Asia for our proprietary assets," said David Urech, Ph.D., Founder and Chief Executive Officer of Numab Therapeutics. "NM28 is a next generation T cell engager for the therapy of mesothelin-expressing tumors based on our MATCHTM-4 platform that allows for bivalent interaction with mesothelin and therefore holds the potential for a larger therapeutic window over conventional T cell engagers."

"Collaborating with the world’s leading technology platforms and biotech companies to develop high-quality drug candidates is a central pillar of our growth strategy. We are looking forward to working with Numab on this very exciting cancer therapy targeting difficult to treat tumors. This alliance is in line with our goal to expand our pipeline with a diverse set of first-in-class multispecific antibodies," said Dr. Jing Lou, Chairman and Chief Executive Officer of 3SBio.

About NM28
NM28 consists of four stabilized and humanized antibody variable domain fragments directed against MSLN, CD3 and human serum albumin (HSA). MSLN is commonly expressed in a variety of tumor cells, including mesothelioma, lung, biliary, ovarian, breast and pancreatic cancer. NM28 is designed to be resistant to the scavenging effect of soluble MSLN shed from tumor cells to improve efficacy, and to discriminate between tumor cells and MSLN-expressing normal cells to improve safety when compared to monovalent T cell engaging approaches targeting MSLN.

Oncotelic’s Dr. Anthony Maida to Present at 2nd Annual TGF-β for Immuno-Oncology Drug Development Summit in January 2022

On December 14, 2021 Oncotelic Therapeutics, Inc. ("Oncotelic" or the "Company") (OTCQB:OTLC), a leading developer of TGF-β therapeutics for oncology and virology, reported that the Company’s Chief Clinical Officer and Board Director, Dr. Anthony Maida, will present at the upcoming 2nd Annual TGF-β for Immuno-Oncology Drug Development Summit (tgf-beta-summit.com), which will take place virtually from January 25, 2022 to January 27, 2022 (Press release, Oncotelic, DEC 14, 2021, View Source [SID1234597108]).

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"There is significant worldwide interest in the clinical application of anti-TGF-β inhibitors, in combination with checkpoint inhibitors, as well as other immuno-oncology and chemotherapeutic options. We look forward to sharing the clinical promise of OT-101 in this setting." noted Dr. Anthony Maida, Chief Clinical Office – Translational Medicine.

TGF-β has been recognized by drug developers, for many years, as holding vast therapeutic potential due to its vital role in cell functioning and signaling. But its complex nature and its ability to be both tumor promoting and tumor suppressing has presented many obstacles for the industry. However, the field appears to be at a tipping point at present, with more candidates moving through clinical evaluation, pointing to an explosion of new data on the way.

"I am excited that we have the opportunity to join other professionals in the field in January to explore novel insights into targeting TGF-β from discovery through clinical testing, and to learn from fellow colleagues such as Genentech, AbbVie, Takeda, and Mestag Therapeutics." noted Dr. Vuong Trieu, CEO and Chairman of Oncotelic.

OT-101 is a first-in-class anti-TGF-β ribonucleic acid ("RNA") therapeutic that has exhibited single agent activity in relapsed/refractory cancer patients in multiple clinical trials. OT-101 has also demonstrated activity against the SARS-CoV-2 virus, the virus that causes COVID-19, and is currently being evaluated in the Company’s C001 clinical trial against hospitalized severe COVID-19 patients. Both tumor cells and SARS-Cov-2 induce TGF-β as part of their immune evasion mechanism.

Consequently, inhibiting TGF-β through therapeutic use of OT-101 carries significant potential to help both cancer and COVID patients in the future.

Recent analyst report for Oncotelic can be accessed here: View Source

Recent Dr. Anthony Maida interview on our clinical program can be accessed here: View Source

Actinium Pharmaceuticals, Inc. Announces 72% MRD Negativity Rate in the Recently Completed Phase 1 Study of Actimab-A in Combination with CLAG-M for Patients with Relapsed or Refractory AML

On December 14, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs reported that updated data from the recently complete Actimab-A and CLAG-M Phase 1 combination trial being conducted at the Medical College of Wisconsin (MCW) was presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH) (Free ASH Whitepaper) that is being held December 11 – 14, 2021 in Atlanta, Georgia and virtually (Press release, Actinium Pharmaceuticals, DEC 14, 2021, View Source [SID1234597107]). This Phase 1 trial was a dose escalation study that evaluated Actimab-A, a CD33 targeting antibody radiation conjugate (ARC) armed with the alpha-emitting radioisotope Actinum-225, combined with CLAG-M (Cladribine, Cytarabine, G-CSF and Mitoxantrone), a salvage chemotherapy regimen for patients fit for intensive therapy.

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Actimab-A + CLAG-M Phase 1 Results:

Complete remissions (CR/CRp) in all dose cohorts
80% overall response rate (CR/CRp/MLFS) in patients receiving less than 4 lines of prior therapy with a total of 10 complete remissions across all four dose cohorts
72% MRD negativity rate determined by flow cytometry compares favorably to 39% MRD negativity rate with CLAG-M alone in MCW’s institutional experience1
60% response rate in patients receiving prior venetoclax therapy including 4 patients that achieved a complete remission
75% of patients proceeded to a bone marrow transplant, excluding patients with prior transplant experience
Median time to best response was 40 days
No 30-day mortality
0.75uCi/kg of Actimab-A identified as recommended Phase 2 dose
Dr. Sameem Abedin, Assistant Professor of Medicine, Medical College of Wisconsin, Division of Hematology and Oncology and Principal Investigator of the study, commented, "We are excited to have completed dose escalation and to report the Phase 1 results of this novel combination of CLAG-M with Actimab-A. AML is known to be highly radio-sensitive, but we cannot treat AML effectively with external radiation sources. Actimab-A solves this issue by directing the potent alpha-emitting radioisotope Actinium-225 at the cellular level inside the body to CD33, which is expressed in virtually all AML patients. Based on our experience with Actimab-A as a single agent, we believed that in combination with CLAG-M it would improve remission rates and the depth of remissions while being safe, given the non-overlapping mechanisms of action. We are very encouraged by the high rates of remissions with MRD negativity, indicating deep responses, and the high number responses seen in patients that had previously failed venetoclax, which is becoming an increasingly larger portion of the AML patient population. Also of note is the high number of patients able to proceed to bone marrow transplant on the study. We look forward to continuing to study this novel combination."

Dr. Avinash Desai, Actinium’s Chief Medical Officer, said, "This study will prove invaluable to our future development of Actimab-A. There are several positive findings from this study including high rates of MRD negativity, strong responses in patients failing venetoclax therapy and high rates of transplant, which all represent future development opportunities. With these data and the recommended Phase 2 dose level determined, we look forward to finalizing our future development strategy for Actimab-A and CLAG-M for patients with relapsed or refractory AML. In addition, these results support our broader strategy of leveraging the differentiated mechanism of targeted radiotherapy utilizing Actimab-A as a backbone in combination with other therapeutic modalities to improve patient outcomes."

Sources:

1)Mushtaq et al. Leukemia & Lymphoma 2020

Actinium Pharmaceuticals, Inc. Reports 2 Remissions and 67% ORR in Patients with a TP53 Mutation in the Phase 1 portion of the Actimab-A Venetoclax Combination Trial in Patients with Relapsed or Refractory AML at the 63rd ASH Annual Meeting

On December 14, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs reported that data from the Phase 1 portion of its Actimab-A and venetoclax combination trial in patients with relapsed or refractory acute myeloid leukemia (AML) was presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH) (Free ASH Whitepaper) that is being held December 11 – 14, 2021 in Atlanta, Georgia and virtually (Press release, Actinium Pharmaceuticals, DEC 14, 2021, View Source [SID1234597105]).

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Patients enrolled in the study to date have been a median age of 64, with 75% of patients having adverse cytogenetics and 50% of patients having received and failed prior venetoclax and hypomethylating agent (HMA) therapy. The trial will continue to dose escalate to a fourth dose cohort of 1.5 μCi/kg to determine the dose for the Phase 2 portion of the study. Key findings from the study to date include:

67% overall response rate (ORR) with 2 remissions in patients with a TP53 mutation
One patient achieving remission has been on study for over 230 days and remains in follow-up after previously failing venetoclax HMA therapy before enrolling on Actimab-A study
No early mortality (< 30 days) in the study to date
"Venetoclax has become a staple therapy for patients with AML, however, patients with relapsed or refractory disease continue to represent a major unmet medical need with median overall survival reported to be 5.5 months and only 3 months in patients that do not respond to venetoclax therapy. After confirming a mechanistic synergy between Actimab-A and venetoclax, we were eager to begin this combination clinical trial. This initial data is highly encouraging thus far, particularly the 2 remissions in patients with a TP53 mutation, which is associated with very poor clinical outcomes. These data support advancing to the Phase 2 portion of the study and based on the high response rates in TP53 patients, we will actively explore a development strategy with this patient population. We look forward to completing the Phase 1 dose escalation portion of this study, to determine the recommended Phase 2 dose so we can continue to advance this novel combination given the high unmet need of the patient population," said Avinash Desai, Actinium’s Chief Medical Officer.

Venetoclax is a targeted therapy for patients with AML that targets Bcl-2, a protein that is overexpressed in certain cancers that enables cancer cells to evade apoptosis or programmed cell death. Actinium evaluated this novel combination after identifying that Actimab-A, via its targeted radiotherapy mechanism, could deplete Mcl-1, a protein that is upregulated in refractory AML cells and mediates resistance to venetoclax. In preclinical studies, Actinium showed that Actimab-A combined with venetoclax, resulted in greater AML cell killing than either Actimab-A or venetoclax alone and resulted in enhanced tumor regression and survival in venetoclax-resistance AML tumor models. The Phase 1/2 trial is a multi-center clinical trial that will enroll up to 38 patients with the Phase 2 portion of the trial to evaluate for safety, minimal residual disease status, disease free survival and overall survival.

Source:

Tenold et al. (2021) Outcomes of Adults with Relapsed/Refractory Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents at a Comprehensive Cancer Center. Front. Oncol. 11:649209. doi: 10.3389/fonc.2021.649209

Synthetic Biologics Announces Planned Transformative Acquisition of VCN Biosciences; Developer of a Novel Oncolytic Virus Platform Targeting Pancreatic and other Solid Tumors

On December 14, 2021 Synthetic Biologics, Inc. (NYSE American: SYN), a diversified clinical-stage company developing therapeutics designed to treat diseases in areas of high unmet need, reported it has signed a definitive agreement to acquire VCN Biosciences, S.L. (VCN), which is developing a new oncolytic adenovirus (OV) platform designed for intravenous (IV) delivery to trigger tumor cell death and promote immune cell infiltration into tumors (Press release, Synthetic Biologics, DEC 14, 2021, View Source [SID1234597103]). Total upfront consideration for the acquisition is $4.7 million in cash plus the assumption of $2.4 million of VCN liabilities. Additionally, VCN will receive shares of Synthetic Biologics’ common stock representing 19.99% of the total shares outstanding of the Company’s common stock. The Company has also agreed to an additional $70.3 million of payments contingent upon the achievement of future milestones, a majority of which are tied to late-stage clinical development and regulatory achievements. The transaction is expected to close during the first quarter of 2022, and is subject to, among other things, the approval by the Spanish government of the Company’s acquisition of VCN under Spain’s Foreign Investment Act and other customary closing conditions. Additional details regarding the transaction are available in the Company’s Current Report on Form 8-K, which has been filed with the Securities and Exchange Commission and is available on the Company’s website.

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Synthetic Biologics, Inc. www.syntheticbiologics.com (PRNewsFoto/Synthetic Biologics, Inc.)

VCN’s technology platform is designed to overcome critical challenges that restrict the development of the majority of OV therapies today. Unlike many OVs that can only be administered by direct intratumoral injection, VCN’s OVs are designed for systemic intravenous administration to target primary as well as metastatic tumors. Once inside the tumor, VCN’s OVs are designed to replicate selectively and aggressively, and to produce hyaluronidase (PH20), an enzyme that digests hyaluronan, a key component of the dense tumor stroma that often plays a crucial role in tumor progression. Degradation of tumor stroma has been shown to diminish a significant physical and immunosuppressive barrier to cancer treatment and thereby improve access to the tumor by additional therapies such as chemo and immuno-therapies. Results from previously completed clinical trials demonstrate that this process can occur for weeks or months following a single intravenous injection with a VCN OV. VCN is seeking to leverage these unique capabilities to address cancers with a high unmet need.

VCN OVs are also designed to be administered intratumorally or intravitreally (in the eye), either as a monotherapy or in combination with standard of care, to treat a wide variety of cancer indications. Combination treatment of VCN OVs with a variety of chemotherapies and immunotherapies such as checkpoint inhibitors and CAR-T cells are in early clinical testing or planned. VCN has the rights to four exclusive patents for proprietary technologies, as well as technologies developed in collaboration with the Virotherapy Group of the Catalan Institute of Oncology (ICO-IDIBELL), with a number of additional patents pending.

VCN’s lead drug candidate, VCN-01, has been evaluated in four Phase 1 clinical trials to date, including in patients with pancreatic cancer, head and neck squamous cell carcinoma, and retinoblastoma (Rb). In a Phase 1 clinical trial, patients with metastatic pancreatic ductal adenocarcinoma (PDAC) received the combination therapy of intravenous VCN-01 with the standard of care chemotherapy Gemcitabine plus Abraxane (G/A). Best results were observed when VCN-01 was administered one week before the first G/A dose. VCN-01 was well tolerated and when combined with G/A demonstrated an improved median overall and progression free survival, as well as a high response rate compared to G/A alone. These data compare favorably with current standard of care and are the basis of a planned Phase 2 clinical trial of the higher dosing level.

VCN-01 is also being studied as a monotherapy in patients with retinoblastoma (RB) who previously failed chemotherapy. Intravitreal administration of VCN-01 produced a complete remission and a reduction of tumors in several patients. These promising outcomes form the basis for an Orphan Drug application with the FDA and are planned to be explored in a larger future clinical trial.

VCN is also developing a next generation Albumin Shield technology platform, VCN-11, which builds upon the pre-clinical and clinical results of VCN-01. VCN-11 incorporates an albumin binding domain in the virus outer shell designed to enable the virus to coat itself with host serum albumin, potentially preventing its inactivation by neutralizing antibodies in the bloodstream en route to the tumor. The addition of the Albumin Shield technology is not expected to interfere with VCN-11’s ability to target tumor cells and may allow for repeated administration to optimize tumor exposure.

Steven A. Shallcross, Chief Executive Officer of Synthetic Biologics, commented, "We are excited to announce this transformative acquisition, as VCN’s platform represents a potentially breakthrough approach to cancer treatment with oncolytic viruses by allowing for systemic delivery, high selectivity and enhanced tumor access. In addition to triggering tumor cell death, these therapies have been shown to elicit a strong anti-tumor immune response. The results of the Phase 1 clinical trial in PDAC, a highly aggressive and lethal malignancy, are very encouraging with respect to tumor response and survival. Significantly, biopsies in these patients confirmed up regulation of tumor immune markers and induction of a robust antitumor immune response, including increased tumor infiltration by cytotoxic T-cells. These results suggest VCN-01 holds significant potential to increase the addressable market for checkpoint inhibitors and CAR-T therapies, as these therapies have historically been less effective immunologically against "cold" tumors like PDAC."

"Based on encouraging results of prior preclinical and clinical trials of VCN-01, we plan to initiate a controlled Phase 2 clinical trial of VCN-01 at multiple centers across the US and EU. There is a significant unmet need for a safe and effective therapy for patients with pancreatic cancer, a condition in which most people diagnosed do not survive more than a year following their initial diagnosis. Based on highly encouraging early clinical results, we also plan to conduct a registrational trial in pediatric patients with advanced Rb. Importantly, this is an underserved patient population and we believe VCN-01 holds tremendous promise to preserve the eyes of these patients, who are typically less than two years old at diagnosis. We believe these trials can be conducted relatively quickly and efficiently. At the same time, we are also evaluating investigator-sponsored studies combining VCN-01 with CAR-T therapies, as well as VCN-01 in other orphan indications such as glioblastoma. We look forward to providing additional details on the timing and design of these trials in the near future."

"VCN was founded by internationally recognized experts in oncolytic adenoviruses for cancer treatment and I will be delighted to welcome them to our team. VCN’s novel therapies allow for a robust and efficient manufacturing process, with an attractive cost structure. The platform is supported by a growing intellectual property (IP) portfolio that provides it patent protection through at least 2030 with additional patents underway that we believe would further strengthen our IP portfolio. Importantly, VCN-01 has been granted Orphan Drug Designation by the European Medicines Agency (EMA), which may provide a number of benefits including up to ten years of market exclusivity. Importantly, we have a strong balance sheet with over $72.1 million of cash as of September 30, 2021, which we believe will provide us significant runway to both support our existing programs, as well as to able to advance VCN-01 and VCN-011 through important milestones that we believe will drive significant shareholder value."

Manel Cascalló, PhD, Chief Executive Officer of VCN, noted, "Joining together with Synthetic Biologics is a significant opportunity as it allows us to partner with an experienced team, well-versed in drug development, manufacturing, and commercialization. We anticipate the combined company will have the financial resources to fund our clinical programs to key value inflection points and we look forward to a successful future together."

Conference Call

Synthetic Biologics will hold a conference call today, December 14, 2021, at 10:00 a.m. Eastern Time. The dial-in information for the call is as follows, U.S. toll free: 1-888-347-5280 or International: +1 412-902-4280. Participants are asked to dial in 15 minutes before the start of the call to register. The call will also be webcast over the Internet at View Source." target="_blank" title="View Source." rel="nofollow">View Source An archive of the call will be available for replay at the same URL, View Source, for 90 days after the call.