Molecular Templates Announces FDA Acceptance of IND Application for MT-6402, a PD-L1-Targeted Engineered Toxin Body Enabled with Proprietary Antigen Seeding Technology

On January 19, 2021 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," "MTEM" or "the Company"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for MT-6402, a next-generation ETB targeting PD-L1 that is enabled with MTEM’s antigen seeding technology (AST) (Press release, Molecular Templates, JAN 19, 2021, View Source [SID1234574098]). ETBs enabled with AST have dual mechanisms of action that include the enzymatic destruction of ribosomes and the delivery of viral class I antigens into the targeted tumor to be processed and presented on its cell surface to induce an antigen specific immune response. MTEM expects to start dosing enrolled subjects in a first-in-human Phase 1 study in relapsed/refractory patients with PD-L1-positive solid tumors in 2Q21.

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The Phase 1 study is planned as a multi-center, open-label, dose escalation and dose expansion trial in the United States and outside of the United States. Patients with confirmed PD-L1 expressing tumors or confirmed PD-L1 expression in the tumor microenvironment will be eligible to screen for enrollment in the clinical trial. Following determination of the maximum tolerated dose (MTD) or recommended Phase 2 dose, expansion cohorts are planned to study MT-6402 as a monotherapy in tumor-specific and tumor-agnostic cohorts.

"We are excited to be advancing MT-6402, a third generation ETB, into the clinic for the treatment of patients with PD-L1-positive cancers. MT-6402 utilizes both our proprietary de-immunized toxin scaffold and antigen seeding technology," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "The PD-1/PD-L1 axis is central to many tumors and targeting that axis with a new mechanism of action has an opportunity to provide meaningful benefit to patients. We look forward to providing an update on the Phase 1 study by year-end 2021."

About MT-6402

MT-6402 is an ETB consisting of a single chain variable fragment (scFv) with affinity for PD-L1, fused to the enzymatically active de-immunized Shiga-like toxin-A subunit (SLTA) and a class I antigen derived from the human cytomegalovirus (HCMV) pp65 protein. MT-6402 was designed to induce potent anti-tumor effects via PD-L1 targeting through multiple mechanisms that may overcome the limitations of the PD-L1 antibodies. In MTEM’s preclinical studies, MT-6402 was found to specifically bind and kill both tumor and immune PD-L1 expressing cells in a manner consistent with SLTA mediated cellular cytotoxicity through ribosomal inactivation, independent of checkpoint inhibition. Additionally, MT-6402 alters the immunophenotype of targeted cells by delivering foreign class I antigen from CMV for presentation in complex with MHC class I, which may provoke a CMV-specific immune response against the targeted cells. Third, MT-6402 may rehabilitate the tumor microenvironment (TME) and allow for immune recognition of tumors by destroying PD-L1-expressing immune cells in the TME through ribosomal inactivation.

FDA Lifts Partial Clinical Hold on PRS-343 Phase 1 Studies

On January 19, 2021 Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer, and other indications, reported that the U.S. Food and Drug Administration (FDA) has lifted the previously announced partial clinical hold on the phase 1 studies of PRS-343 (Press release, Pieris Pharmaceuticals, JAN 19, 2021, View Source [SID1234574097]). As previously guided, the Company intends to move into a proof-of-concept study of PRS-343 in gastroesophageal cancer.

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"It has been rewarding to see the impact of PRS-343 on the lives of patients in these studies. Data continue to be encouraging, and the clinical benefit linked to single-agent activity that we have seen attests to the potential of this therapy and, more broadly, our localized 4-1BB agonism approach," said Stephen S. Yoder, President and Chief Executive Officer of Pieris. "We are excited to advance this program into the proof-of-concept phase and look forward to sharing more details about the study later this quarter."

Advaxis Announces Receipt of Funding Milestone Payment Under ADXS-HER2 Licensing Agreement with OS Therapies

On January 19, 2021 Advaxis, Inc. (NASDAQ: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported that the Company has received the first milestone payment related to its licensing agreement for ADXS31-164, now known as OST-HER2, to OS Therapies for evaluation in the treatment of osteosarcoma in humans (Press release, Advaxis, JAN 19, 2021, View Source [SID1234574096]).

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Under the terms of the amended and restated license agreement, OS Therapies, in collaboration with the Children’s Oncology Group (COG)1, is responsible for the conduct and funding of a clinical study evaluating OST-HER2 in recurrent, completely resected osteosarcoma. OS Therapies secured funding to support this research, triggering the first milestone payment. Under the agreement, Advaxis will receive additional clinical, regulatory, and sales-based milestone payments as well as royalties on future product sales. Additional details of the financial terms have not been disclosed.

"We are pleased that OS Therapies is now in position to initiate human clinical trials of OST-HER2 in osteosarcoma," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "ADXS31-164, which had been conditionally approved in the U.S. for the adjuvant treatment of osteosarcoma in canines, has the potential to provide a new treatment option for human osteosarcoma patients, particularly in children with this challenging disease for which there are few therapeutic options. As Advaxis is currently focused on developing our ADXS-HOT neoantigen-directed off-the-shelf therapeutics, with recent encouraging data in non-small cell lung cancer, we hope that OS Therapies can successfully explore the clinical potential of OST-HER2 in osteosarcoma, building on an earlier Phase 1 clinical trial performed by us where ADXS31-164 was safe and tolerable in humans."

Paul Romness, Chief Executive Officer of OS Therapies, said, "The OS Therapies mission is to develop and commercialize new therapeutics for the treatment of osteosarcoma, a deadly and extremely underserved pediatric cancer. We are excited to be in position to evaluate OST-HER2 in this indication, as it has been safe and effective in treating osteosarcoma in dogs, a natural model that is the similar to humans, and to be safe and tolerable in humans. Our goal is to stimulate the immune system to specifically target tumor dysplastic cells that express HER2, which is a common genetic mutation found in osteosarcoma. We believe that targeting Osteosarcoma and other solid tumors with OST-HER2 holds potential to impact the treatment paradigm."

Osteosarcoma is an aggressive cancerous tumor that forms in bone. Although it is rare, osteosarcoma is the most common type of bone cancer, and is most frequently found in children and young adults. Current treatment options are limited and there have been no new treatment options in more than thirty years.

1 The Children’s Oncology Group (www.childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research with over 10,000 experts worldwide working in over 200 COG member institutions. COG’s mission is to improve the cure rate and outcome for all children with cancer.

Myriad Genetics Receives Reimbursement for BRACAnalysis® Diagnostic System in Japan

On January 19, 2021 In an announcement that will help more people with advanced prostate and pancreatic cancers in Japan, Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in genetic testing and precision medicine, reported that it will receive reimbursement for its BRACAnalysis Diagnostic System, which helps physicians determine whether certain patients will qualify and potentially benefit from treatment with the PARP inhibitor, Lynparza (olaparib) (Press release, Myriad Genetics, JAN 19, 2021, View Source [SID1234574095]). BRACAnalysis was approved by Japan’s Ministry of Health, Labour and Welfare (MHLW) in October 2020 as a companion diagnostic for these indications and the reimbursement decision is now in effect.

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"BRACAnalysis continues to be the gold standard for germline BRCA1 and BRCA2 testing around the globe," said Nicole Lambert, president of Myriad Genetic Laboratories. "Our goal is to continue to expand patient access to the proven benefits of genetic testing and help physicians combat even the most difficult to treat cancers."

Myriad estimates there are more than 78,000 cases of prostate cancer and 40,000 cases of pancreatic cancer per year in Japan. With the reimbursement decision, approximately 20,000 patients in Japan will now qualify to receive genetic testing. BRACAnalysis was previously approved in Japan to identify patients with ovarian and breast cancer who have a germline BRCA mutation and are eligible for treatment with Lynparza. BRACAnalysis is the only germline test for BRCA1 and BRCA2 mutations to receive regulatory approval in Japan.

"Now that BRACAnalysis is available in Japan to assess the presence of BRCA1 or BRCA2 in deleterious or suspected deleterious mutations, more patients with prostate and pancreatic cancer will have access to advanced options for treatment," said Hiroji Uemura, M.D., Ph.D., Professor, Department of Urology and Renal Transplantation, Yokohama City University Medical Center.

"As physicians, we are excited to use BRACAnalysis to identify those patients who may need those advanced treatments, and to continue improving health outcomes in the fight against those cancers," added Hideki Ueno, M.D., Ph.D., Medical Director, Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital."

Myriad has been collaborating with AstraZeneca since 2007 on the development of companion diagnostics for Lynparza. Lynparza is a trademark of AstraZeneca. Lynparza is jointly developed and commercialized by AstraZeneca and MSD (known as Merck & Co., Inc. in the United States and Canada). Additionally, Myriad has partnered with SRL Inc., a subsidiary of H.U. Group Holdings, Inc. to expand the commercialization of the BRACAnalysis Diagnostic System in Japan.

According to World Cancer Research Fund, pancreatic cancer is the 12th most common cancer worldwide and Japan ranks third in the world for highest rates of incidence, according to the World Health Organization. Additionally, in Japan, prostate cancer is estimated to account for 18% of cancers diagnosed in men, according to the International Agency for Research on Cancer.

About the BRACAnalysis Diagnostic System
BRACAnalysis is a diagnostic system that classifies a patient’s clinically significant variants (DNA sequence variations) in the germline BRCA1 and BRCA2 genes. Variants are classified into one of the five categories; "Deleterious," "Suspected Deleterious," "Variant of Uncertain Significance," "Favor Polymorphism," or "Polymorphism." Once the classification is completed, the results are sent to medical personnel in Japan for determining the eligibility of patients for treatment with Lynparza.

About SRL
Since the establishment in 1970, SRL, Inc., a member of the H.U. Group Holdings, Inc., Japan-based leading healthcare group, has been providing comprehensive testing services as the largest commercial clinical laboratory in Japan. SRL carries out nearly 400,000,000 tests per year, covering a wide range of testing services including general/emergency testing, esoteric/research testing, companion diagnostics tests, genomic analysis, and etc. For more information, please visit View Source

Soligenix Announces Investor Webcast Event: U.S. Commercialization of SGX301 in the Treatment of Cutaneous T-Cell Lymphoma

On January 19, 2021 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported that it will be hosting an Investor Webcast Event on Tuesday, January 26, 2021 from 2:30-4:00 PM Eastern Standard Time (EST) regarding United States (U.S) commercial planning for SGX301 in the treatment of Cutaneous T-Cell Lymphoma (CTCL) (Press release, Soligenix, JAN 19, 2021, View Source [SID1234574094]).

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SGX301 (synthetic hypericin) is a novel first-in-class photodynamic therapy for first-line treatment of early stage CTCL. In the recently completed pivotal Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) trial, SGX301 achieved a statistically significant treatment response rate (p=0.04) in the primary endpoint after just 6 weeks (Cycle 1) of therapy when compared to placebo. This positive treatment response continued to significantly improve with extended SGX301 treatment in the open-label treatment cycles after 12 weeks (Cycle 2) and 18 weeks (Cycle 3) total treatment, reinforcing the positive SGX301 primary endpoint treatment response demonstrated in Cycle 1. In addition, SGX301 has demonstrated a statistically significant response in both patch and plaque lesions through 12 weeks of treatment (Cycle 2), highlighting the unique benefit of using visible light with its deeper skin penetration. SGX301 was well tolerated throughout the study and no mutagenic risks have been identified, unlike other second-line or off-label treatments, including other phototherapies, which utilize ultraviolet light. The Company believes SGX301 has compelling competitive advantages over existing therapies for early stage CTCL and represents a significant near-term commercial opportunity.

Conference Call Tuesday, January 26, 2021 from 2:30-4:00 PM EST

The Company will share information about its commercialization plans in the U.S. for SGX301 on Tuesday, January 26, 2021. A question and answer (Q&A) session with the featured experts and management will follow the presentations. If you would like to ask a question during the Q&A, please submit your request via email to [email protected] at least 15 minutes prior to the scheduled start of the call.

Live Event: View Source

An mp4 recording of the presentation will be archived for 30 days following the event.

This Investor Event will include presentations from the following:

Dr. Ellen Kim, Medical Director, Dermatology Clinic, Perelman Center for Advanced Medicine and Lead Investigator of the FLASH study;

Dr. Brian Poligone, Director, Rochester Skin Lymphoma Medical Group and lead enroller in the FLASH study;

Mr. Michael Young, Principal, biomedwoRx: Life Sciences Consulting and member of the Cutaneous Lymphoma Foundation Board of Directors;

Mr. Dan Ring, Vice President, Business Development & Strategic Planning of Soligenix; and

Dr. Christopher J. Schaber, President and Chief Executive Officer of Soligenix.

About Cutaneous T-Cell Lymphoma (CTCL)

CTCL is a class of non-Hodgkin’s lymphoma (NHL), a type of cancer of the white blood cells that are an integral part of the immune system. Unlike most NHLs which generally involve B-cell lymphocytes (involved in producing antibodies), CTCL is caused by an expansion of malignant T-cell lymphocytes (involved in cell-mediated immunity) normally programmed to migrate to the skin. These malignant cells migrate to the skin where they form various lesions, typically beginning as patches and may progress to raised plaques and tumors. Mortality is related to the stage of CTCL, with median survival generally ranging from about 12 years in the early stages to only 2.5 years when the disease has advanced. There is currently no cure for CTCL. Typically, CTCL lesions are treated and regress but usually return either in the same part of the body or in new areas.

CTCL constitutes a rare group of NHLs, occurring in about 4% of the approximate 700,000 individuals living with the disease. It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of CTCL that it affects over 25,000 individuals in the U.S., with approximately 3,000 new cases seen annually.

About SGX301

SGX301 (synthetic hypericin) is a novel first-in-class photodynamic therapy utilizing safe visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a potent photosensitizer that is topically applied to skin lesions, is taken up by the malignant T-cells, and then activated by fluorescent light 16 to 24 hours later. The use of visible light in the red-yellow spectrum has the advantage of penetrating more deeply into the skin (much more so than ultraviolet light) and therefore potentially treating deeper skin disease and thicker lesions. This treatment approach avoids the risk of secondary malignancies (including melanoma) inherent with the frequently employed DNA-damaging drugs and other phototherapy that are dependent on ultraviolet exposure. Combined with photoactivation, hypericin has demonstrated significant anti-proliferative effects on activated normal human lymphoid cells and inhibited growth of malignant T-cells isolated from CTCL patients. In a published Phase 2 clinical study in CTCL, patients experienced a statistically significant (p=0.04) improvement with topical hypericin treatment whereas the placebo was ineffective. SGX301 has received orphan drug and fast track designations from the FDA, as well as orphan designation from the European Medicines Agency (EMA).

The Phase 3 FLASH trial enrolled a total of 169 patients (166 evaluable) with Stage IA, IB or IIA CTCL. The trial consists of three treatment cycles. Treatments were administered twice weekly for the first 6 weeks and treatment response was determined at the end of the 8th week of each cycle. In the first double-blind treatment cycle, 116 patients received SGX301 treatment (0.25% synthetic hypericin) and 50 received placebo treatment of their index lesions. A total of 16% of the patients receiving SGX301 achieved at least a 50% reduction in their lesions (graded using a standard measurement of dermatologic lesions, the CAILS score) compared to only 4% of patients in the placebo group at 8 weeks (p=0.04) during the first treatment cycle (primary endpoint). SGX301 treatment in the first cycle was safe and well tolerated.

In the second open-label treatment cycle (Cycle 2), all patients received SGX301 treatment of their index lesions. Evaluation of 155 patients in this cycle (110 receiving 12 weeks of SGX301 treatment and 45 receiving 6 weeks of placebo treatment followed by 6 weeks of SGX301 treatment), demonstrated that the response rate among the 12-week treatment group was 40% (p<0.0001 vs the placebo treatment rate in Cycle 1). Comparison of the 12-week and 6-week treatment groups also revealed a statistically significant improvement (p<0.0001) between the two groups, indicating that continued treatment results in better outcomes. SGX301 continued to be safe and well tolerated. Additional analyses also indicated that SGX301 is equally effective in treating both plaque (response 42%, p<0.0001 relative to placebo treatment in Cycle 1) and patch (response 37%, p=0.0009 relative to placebo treatment in Cycle 1) lesions of CTCL, a particularly relevant finding given the historical difficulty in treating plaque lesions in particular.

The third (optional) treatment cycle (Cycle 3) was focused on safety and all patients could elect to receive SGX301 treatment of all their lesions. Of note, 66% of patients elected to continue with this optional compassionate use / safety cycle of the study. Of the subset of patients that received SGX301 throughout all 3 cycles of treatment, 49% of them demonstrated a treatment response (p<0.0001 vs patients receiving placebo in Cycle 1). Moreover, in a subset of patients evaluated in this cycle, it was demonstrated that SGX301 is not systemically available, consistent with the general safety of this topical product observed to date. At the end of Cycle 3, SGX301 continued to be well tolerated despite extended and increased use of the product to treat multiple lesions. Follow-up visits were completed in Q4 2020, and data lock and final analyses remain ongoing.

Overall safety of SGX301 is a critical attribute of this treatment and was monitored throughout the three treatment cycles (Cycles 1, 2 and 3) and the 6-month follow-up period. SGX301’s mechanism of action is not associated with DNA damage, making it a safer alternative than currently available therapies, all of which are associated with significant and sometimes fatal, side effects. Predominantly these include the risk of melanoma and other malignancies, as well as the risk of significant skin damage and premature skin aging. Currently available treatments are only approved in the context of previous treatment failure with other modalities and there is no approved front-line therapy available. Within this landscape, treatment of CTCL is strongly motivated by the safety risk of each product. SGX301 potentially represents the safest available efficacious treatment for CTCL. With no systemic absorption, a compound that is not mutagenic and a light source that is not carcinogenic, there is no evidence to date of any potential safety issues.

The Phase 3 CTCL clinical study was partially funded by the National Cancer Institute via a Phase II SBIR grant (#1R44CA210848-01A1) awarded to Soligenix, Inc.