On August 30, 2020 CStone Pharmaceuticals (SUZHOU) Co., Ltd. ("CStone", HKEX: 2616) reported that the US Food and Drug Administration (FDA) has completed their review of the Investigational New Drug (IND) application for anti-PD-L1 monoclonal antibody sugemalimab (CS1001) monotherapy in the relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (R/R ENKTL) with study may proceed (SMP) letter received (Press release, CStone Pharmaceauticals, AUG 30, 2020, View Source [SID1234564157]).

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!

Sugemalimab is an investigational fully human, full-length anti-PD-L1 monoclonal antibody developed by CStone. Compared with other drugs of the same class, sugemalimab has a lower risk of immunogenicity and potential toxicities in patients. CS1001-201 is a single-arm, multicenter pivotal Phase II clinical study designed to evaluate sugemalimab monotherapy in R/R ENKTL. The IND clearance indicates that the ongoing CS1001-201 study in China will be extended to the US.

ENKTL is a subtype of mature T cell and NK cell lymphoma. Epidemiology of the disease is characterized by higher incidence rates in Asia than in Europe or North America. In China, ENKTL accounts for approximately 6% of all lymphoma cases[1]. R/R ENKTL is highly malignant and aggressive, and has a poor prognosis. Patients with R/R ENKTL lack effective salvage treatments if standard L-asparaginase-based regimens fail, and do not respond well to traditional treatments. For these patients, clinicians almost run out of treatment choices because the disease progresses rapidly with an extremely short overall survival (OS) as indicated by historically reported 1-year OS rate <20%[2]. The currently approved targeted monotherapy in China has a complete response (CR) rate of approximately 6%[3],[4]. There are vast unmet medical needs in this patient population of which the first-line treatment has failed. Sugemalimab is expected to provide new treatment options for these patients.

Dr. Jason Yang, Chief Medical Officer of CStone, commented: "For the treatment of ENKTL, CR rate is a critical outcome measure. Data reported for CS1001-201 study on 2019 ASH (Free ASH Whitepaper) meeting shows that sugemalimab demonstrated a CR rate of 33.3% with a durable response, an objective response rate (ORR) of 43.3%, and 1-year OS rate of 72.4%. These results represent a major breakthrough compared to current treatment options and support sugemalimab as a potential conditioning regimen for hematopoietic stem cell transplantation. We will work closely with the US FDA and the National Medical Products Administration (NMPA), to bring sugemalimab to R/R ENKTL patients worldwide soon."

Overview of the CS1001-201 trial

CS1001-201 is a single-arm, multicenter Phase II clinical study designed to evaluate sugemalimab monotherapy in R/R ENKTL. The primary endpoint of the trial is ORR assessed by an independent radiological review committee.

According to updated results reported at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, as of October 8, 2019, a total of 32 patients with R/R ENKTL were enrolled in the study. All patients received sugemalimab 1200 mg intravenously every 3 weeks until disease progression or intolerable toxicity. The median duration of follow-up was 6.54 months (range, 0.72–15.64).

Preliminary efficacy data

Sugemalimab demonstrated robust efficacy with a high CR rate and durable response in R/R ENKTL patients:

Among the 30 efficacy-evaluable patients, the investigator-assessed ORR was 43.3%
10 patients (33.3%) achieved CR and were still in remission
3 patients (10.0%) achieved partial response (PR), and 1 additional patient achieved PR after pseudo-progression
The median duration of response (DoR) was not reached, and the maximum DoR was 10.9+ months
The 1-year OS was 72.4% (95% CI: 52.0%–85.2%)
Safety data

Sugemalimab was well tolerated in patients with R/R ENKTL:

30 patients (93.8%) reported treatment-emergent adverse events (TEAEs), 24 patients (75.0%) reported treatment-related adverse event (TRAEs), of which 3 (9.4%) had Grade >3 TRAEs
Grade 5 AEs were reported in 3 patients (9.4%), and none were assessed as related to sugemalimab
Immune-related AEs (irAEs) were reported in 5 patients (15.6%); except for one case of Grade 3 rash, all irAEs were Grade 1 in severity
TEAEs that led to permanent treatment discontinuation occurred in 4 patients (12.5%)
No deaths due to AEs were assessed as related to sugemalimab
About Sugemalimab

Sugemalimab is an investigational anti-PD-L1 monoclonal antibody discovered by CStone. Authorized by the U.S.-based Ligand Corporation, sugemalimab is developed by the OmniRat transgenic animal platform, which can generate fully human antibodies in one stop. As a fully human, full-length anti-PD-L1 monoclonal antibody, sugemalimab mirrors the natural G-type immunoglobulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities in patients, a unique advantage over similar drugs.

Sugemalimab has completed a Phase I dose-escalation study in China. During Phase 1a and 1b stages of the study, sugemalimab showed good antitumor activity and good tolerability in multiple tumor types.

Currently, sugemalimab is being investigated in a number of ongoing clinical trials. In addition to a Phase I bridging study in the U.S., the clinical program in China includes one multi-arm Phase Ib study for several tumor types, one Phase II registrational study for lymphoma, and four Phase III registrational studies, respectively, for stage III/IV NSCLC, gastric cancer, and esophageal cancer.

On August 29, 2020 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO) reported that the US Food and Drug Administration, FDA, has granted priority review for Oncopeptides´ New Drug Application seeking approval of melflufen (INN melphalan flufenamide), in combination with dexamethasone for the treatment of adult patients with multiple myeloma whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent and one anti-CD-38 monoclonal antibody, (i.e., triple-class refractory multiple myeloma patients) (Press release, Oncopeptides, AUG 29, 2020, View Source [SID1234564153]). The FDA has set a PDUFA-date (Prescription Drug User Fee Act), which is the target date for their review of the New Drug Application, to February 28, 2021.

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!

The submission is based on the results from the pivotal phase 2 study HORIZON, evaluating intravenous melflufen in combination with dexamethasone in patients with relapsed refractory multiple myeloma, (RRMM).

"This is very exciting news. It is an important milestone for Oncopeptides, and a major step in making melflufen available for patients with multiple myeloma, who desperately need new treatment options", says Marty J Duvall, CEO of Oncopeptides AB. "I am looking forward to a continuing dialogue with the FDA while we make the product available to RRMM patients in the US through an expanded access program, in an FDA approved trial called sEAPort."

A Priority Review designation means that FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review). They will direct overall resources to the evaluation of applications for drugs that, "if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications".

About melflufen
Melflufen (INN melphalan flufenamide) is a first in class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately hydrolyzed by peptidases to release an entrapped hydrophilic alkylator payload. Aminopeptidases are overexpressed in tumor cells and are even more pronounced in advanced cancers and tumors with a high mutational burden. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies. In the pivotal phase 2 HORIZON study melflufen plus dexamethasone demonstrated encouraging efficacy and a clinically manageable safety profile in heavily pretreated patients with relapsed refractory multiple myeloma, with primarily hematologic Adverse Events (AE) and a low incidence of non-hematologic AEs.

On August 28, 2020 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light activated Photo Dynamic Compounds ("PDCs") and their associated drug formulations intended to safely and effectively destroy various cancers, bacteria and viruses reported its unaudited interim consolidated condensed 2Q2020 financial statements (Press release, Theralase, AUG 28, 2020, View Source [SID1234568566]).

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!

Financial Highlights:

Total revenue for the six-month period ended June 30, 2020, decreased to $293,453 from $370,436 for the same period in 2019, a 21% decrease.

In Canada, revenue decreased 23% to $255,146 in 2020 from $333,047 in 2019. In the US, revenue decreased 49% to 12,267 in 2020 from $23,926 in 2019. International revenue increased 93% to $26,041 for 2020 from $13,463 in 2019. The decrease in total revenue in 2020 is primarily attributed to the COVID-19 pandemic as a majority of health care practitioners elected to temporarily close their practices and place any purchasing decisions on temporary or permanent hold

Cost of sales for the six-month period ended June 30, 2020 was $230,095 which included a one-time provision for inventory of $77,075 resulting in an adjusted cost of sales of $153,020 or 52% of revenue with an adjusted gross margin of $140,433 or 48% of revenue, compared to a cost of sales of $267,644 or 72% of revenue in 2019, resulting in a gross margin of $102,792 or 28% of revenue. Cost of sales is represented by the following costs: raw materials, subcontracting, direct and indirect labour and the applicable share of manufacturing overhead. The gross margin decrease, as a percentage of sales, year over year, is attributed to decreased sales and fixed production salaries for the TLC-1000 and TLC-2000 product lines.

Selling expenses for the six-month period ended June 30, 2020 decreased to $229,998, from $344,501 in 2019, a 33% decrease. The decrease in selling expenses is primarily due to the restructuring of the Canadian and US sales and marketing departments, resulting in the resignation and/or termination of certain sales and marketing personnel and reduced travel expenditures due to the COVID-19 pandemic.

Administrative expenses for the six-month period ended June 30, 2020 decreased to $965,824 from $1,062,087 in 2019, a 9% decrease. The decrease in administrative expenses is primarily attributed to decreased spending on general and administrative expenses (48%) and administrative salaries (58%) due to the restructuring of the administrative department, resulting in the termination of certain administrative personnel.

Net research and development expenses for the six-month period ended June 30, 2020 increased to $2,219,057 from $1,303,375 in 2019, a 70% increase. The increase in research and development expense are primarily due to increased expenses for operating the Phase II Non-Muscle Invasive Bladder Cancer ("NMIBC") Clinical Study ("Study II"). Research and development expenses represented 67% of the Company’s operating expenses for the six-month period ended June 30, 2020 and represent investment into the research and development of the Company’s PDT technology.

The net loss for the six-month period ended June 30, 2020 was $3,267,624 which included $642,709 of net non-cash expenses (i.e.: amortization, stock-based compensation expense and foreign exchange gain/loss). This compared to a net loss for the same period in 2019 of $2,612,268 which included $194,361 of net non-cash expenses.

The PDT division represented $2,385,877 of this loss (73%) for the six-month period ended June 30, 2020.

The increase in net loss is primarily attributed to the following:

Increased investment in the clinical expense of Study II.
Decreased sales of the TLC-1000 and TLC-2000 due to market uncertainty directly attributable to the COVID-19 pandemic.
Operational Highlights:

COVID-19 Update: Theralase continues to experience reduced sales due to the ongoing COVID-19 pandemic and has taken actions to reduce expenses by eliminating non-essential personnel and imposing a temporary hiring freeze, to be lifted, subject to the Canadian and United States economies demonstrating recovery from COVID-19.

Clinical Study Site Status: Theralase has successfully launched 4 Canadian study sites with 1 additional Canadian clinical study site in advanced negotiation.

Three out of four Canadian clinical study sites have re-commenced new patient enrollment and treatment in Study II, specifically:

MUHC currently remains closed due to COVID-19, for new patient enrollment and treatment; however, patients who have already been enrolled and treated and who are eligible for second treatment will receive their second treatment.

Theralase is in advanced discussions to launch a number of US based clinical study sites later in the year, subject to the United States economy recovering from the COVID-19 pandemic. The US based Trial Management Organization ("TMO") could potentially launch 4 clinical study sites in 4Q2020 and commence Study II patient enrollment and treatment as early as 1Q2021.

Study II Interim Data: Study II enrolled and treated 12 patients, with the following results:

Of the 7 patients, who demonstrated a Response to the Study Treatment defined as negative cystoscopy (no evidence of cancer in their bladders) or negative urine cytology (no evidence of the urothelial carcinoma cells in their urine)) at 90 days post initial treatment:

43% achieved a Complete Response ("CR") (negative cystoscopy and negative urine cytology)
43% achieved a Response (negative cystoscopy and positive or suspicious cytology)
14% achieved a Response (suspicious cystoscopy and negative cytology)
Additional Oncology Targets. The Company has demonstrated significant anti-cancer efficacy of Rutherrin (patented formulation of the Company’s lead PDC (TLD-1433) and transferrin), when activated by laser light or radiation treatment across numerous preclinical models; including: Glio Blastoma Multiforme ("GBM") and Non-Small Cell Lung Cancer ("NSCLC").

The Company is planning to commence toxicology studies with Rutherrin to determine the maximum recommended human dose of the drug, when administered systemically into the human body, via intravenous injections. Due to the limitations of using laser light to activate Rutherrin in deep oncological targets, Theralase’s research strongly suggests that Rutherrin may be activated with radiation therapy, which is able to increase the ‘tumour’s damage zone’ and the effectiveness of the anti-cancer therapy beyond the reach of light in the body.

Additional Virus Targets. Theralase executed a Sponsored Research Agreement ("SRA") with the University of Manitoba ("UM") Medical Microbiology department to commence development of a coronavirus vaccine and therapy utilizing Theralase’s patented and proprietary PDCs. According to the SRA, UM will conduct experiments in conjunction with Theralase for the research and development of a coronavirus vaccine and therapeutic to be further evaluated in animal then human clinical testing in 2021.

The primary objective of the SRA executed between the UM and Theralase is to investigate the ability of Theralase’s lead PDC in the destruction of a variety of viruses; including: H1N1 Influenza, Zika, coronaviruses and of course COVID-19. The secondary objective is to optimize the concentration of PDC required, the activation methodology and how to potentially administer the treatment to humans to be used as a vaccine (prevention of a patient from contracting COVID-19) and as a therapeutic (treatment of a patient who has already contracted COVID-19). The research is primarily directed to in-vitro (Petri dish of viruses) analysis, but based on these initial experiments, Theralase hopes to expand the work, in conjunction with Dr. Coombs, to in-vivo (small animal) analysis, toxicology (optimized doses for human delivery) and finally human testing through Phase I (safety), Phase II (efficacy) and eventually Phase III (efficacy in a larger population) clinical studies. If successful through a Phase III clinical study, and with the successful regulatory approval of Health Canada, the technology could be commercialized across Canada for the benefit of all Canadians.*

* The Company does not claim or profess that they have the ability to treat, cure or prevent the contraction of the COVID-19 Coronavirus.

About Study II

Study II utilizes the Therapeutic Dose (0.70 mg/cm2) of TLD-1433 and is focused on the enrollment and treatment of approximately 100 Bacillus Calmete Guérin ("BCG")-Unresponsive NMIBC patients presenting with Carcinoma In-Situ ("CIS") in approximately 20 clinical study sites located in Canada and the US.

Study II has a:

Primary endpoint of efficacy (defined by Complete Response ("CR")) at any point in time
Secondary endpoint of duration of CR at 360 days post-initial CR (approximately 450 days post initial Study treatment)
Tertiary endpoint of safety measured by incidence and severity of Adverse Events ("AEs") grade 4 or higher that do not resolve within 450 days post-initial treatment
"For single-arm trials of patients with BCG-unresponsive disease, the FDA defines CR as at least one of the following:

Negative cystoscopy and negative (including atypical) urine cytology
Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology
For intravesical therapies without systemic toxicity, the FDA includes, in the definition of a CR, negative cystoscopy with malignant urine cytology, if cancer is found in the upper tract or prostatic urethra and random bladder biopsies are negative.
Intravesical instillation does not deliver the investigational drug to the upper tract or prostatic urethra; therefore, the development of disease in these areas cannot be attributed to a lack of activity of the investigational drug. Thus, sponsors can consider patients with new malignant lesions of the upper tract or prostatic urethra, who have received intravesical therapy to have achieved a CR in the primary analysis; however, sponsors should record these lesions and conduct sensitivity analyses in which these patients are not considered to have achieved a CR."1

On August 28, 2020 NRG Oncology reported that A practice-changing study, NRG Oncology clinical trial NRG-RTOG 9802, has demonstrated, for the first time, a survival benefit of adjuvant chemotherapy following radiotherapy over radiotherapy alone in certain subgroups of patients with high-risk, low-grade glioma (WHO classification: LGG, grade II), a type of brain tumor that originates from glial cells (Press release, NRG Oncology, AUG 28, 2020, https://www.nrgoncology.org/Home/News/Post/comprehensive-genomic-analysis-in-NRG-Oncology-RTOG-9802 [SID1234564209]).

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!

The study results, published in a recent issue of the Journal of Clinical Oncology, sought to determine the prognostic and predictive impact of WHO-defined molecular subgroups and corresponding molecular alterations, known as IDH1/2 mutations, in people with the disease. LGG patients display highly variable survival outcomes depending on which molecular subgroup they are in. These subgroups are: IDH-wild type, IDH-mutant/1p19q non-codeleted, and IDH-mutant/1p19q codeleted. Genetic mutations were determined by testing patients’ tissue samples through immunohistochemistry and/or deep sequencing.

A total of 116 of 251(46%) enrolled "high-risk" patients with LGG from the two treatment arms had adequate tissues available for genomic analyses using multiple platforms. After neuropathology review, representative areas (70% tumor) were selected for DNA isolation. Of the eligible patients successfully profiled for the WHO-defined molecular groups, 26 of them (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37 (35%) were IDH-mutant/codeleted. Treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer progression-free survival (HR, 0.32; P =.003; HR, 0.13; P < .001) and overall survival (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either progression-free survival or overall survival was observed with the addition of PCV in the IDH-wild-type subgroup.

"Our study is the first to our knowledge to demonstrate the predictive value of the WHO-defined molecular subgroups in a practice-changing phase III clinical trial of high-risk grade II glioma in correlation to overall survival with long-term follow-up data," said the study’s lead author Arnab Chakravarti, MD, professor and chair of the Department of Radiation Oncology at The Ohio State University Comprehensive Cancer Center, the Klotz Family Chair of Cancer Research, and Director of the Brain Tumor Program. "Our evidence suggests that IDH mutation status could serve as the primary predictor of response to PCV in addition to radiotherapy in high-risk LGGs and is a more accurate predictor of response than historical histopathological classifications."

Importantly, the analysis supports the notion that patients with IDH-mutant high risk LGG, regardless of codeletion status, receive benefit from the addition of PCV. "This study can now help clinicians interpret the results within the context of the altered molecular landscape and serve as a basis for survival times for the design of future high-risk LGG clinical trials," added Dr. Chakravarti.

NRG-RTOG 9802 was supported by National Cancer Institute (NCI) Grants No. U10CA21661, U10CA180868, U10CA180822, UG1CA189867, and U10CA37422 (NRG Oncology/RTOG); NCI Grant No. P30 CA016058; NCI Grants No.R01CA108633, R01CA169368, RC2CA148190, and U10CA180850-01 (A.C.); a Brain Tumor Funders Collaborative Grant (A.C.); The Ohio State University Comprehensive Cancer Center (A.C.); and Cancer Therapy Evaluation Program of the NCI Grant No. NRG-BN-TS002 (A.C.and E.H.B.).

On August 28, 2020 CohBar, Inc. (NASDAQ: CWBR) (the "Company"), a clinical stage biotechnology company developing mitochondria based therapeutics to treat chronic diseases and extend healthy lifespan, reported the closing of its previously announced underwritten public offering of 12,300,000 units at a price to the public of $1.22 per unit (Press release, CohBar, AUG 28, 2020, View Source [SID1234564156]). Each unit consists of one share of the Company’s common stock and one warrant to purchase 0.75 of a share of common stock at a per share exercise price of $1.44. In addition, the underwriters partially exercised the over-allotment option for warrants to purchase an additional 1,383,750 shares. The warrants are exercisable for five years from the closing date of the offering. The aggregate gross proceeds from this offering were approximately $15.0 million, before deducting underwriting discounts and commissions and estimated offering expenses.

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!

Roth Capital Partners acted as sole book-running manager for the offering and Brookline Capital Markets, a division of Arcadia Securities, LLC, and WBB Securities acted as co-managers.

The securities were issued pursuant to an effective shelf registration statement filed with the Securities and Exchange Commission (SEC) on November 22, 2017. A final prospectus supplement and accompanying prospectus relating to the offering were filed with the SEC and are available on the SEC’s website at www.sec.gov. Copies of the prospectus supplement, together with the accompanying prospectus, can be obtained at the SEC’s website at www.sec.gov or from Roth Capital Partners, 888 San Clemente, Newport Beach, CA 92660, Attn: Prospectus Department, telephone: 800-678-9147.

This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.