Theralase Launches Sixth Clinical Study Site in the US for Phase II Bladder Cancer Clinical Study

On March 25, 2021 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company focused on the research and development of light activated Photo Dynamic Compounds ("PDC") and their associated drug formulations used to safely and effectively destroy various cancers, bacteria and viruses reported that Urology San Antonio ("USA") has received site Institutional Review Board ("IRB") approval to commence a Pivotal Phase II Non-Muscle Invasive Bladder Cancer ("NMIBC") Clinical Study to enroll and treat patients with Bacillus Calmette Guerin("BCG")-Unresponsive Carcinoma In-Situ ("CIS") or who are intolerant to BCG Therapy ("Study II") (Press release, Theralase, MAR 25, 2021, View Source [SID1234577149]).

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This marks the sixth US Clinical Study Site ("CSS") that has obtained site IRB approval through a central IRB. Theralase is at different stages with additional US clinical study sites that are expected to launch in 2Q21 and 3Q21.

Urology San Antonio is the largest urology practice in South Texas with multiple locations offering care for men and women experiencing complications of the urinary system. Their subspecialists develop incredible expertise in different aspects of urologic care and can offer patients treatment options and guidance not commonly seen in a community urology practice. Dr. Daniel Saltzstein MD will be the Study II Principal Investigator for this site.

To date 16 patients have been treated in Study II. The Company has now launched 5 CSS’s in Canada and 6 in the US for patient enrollment and treatment under Study II clinical study guideline.

Shawn Shirazi PhD, Chief Executive Officer, Theralase, stated, "It is exciting to see Theralase hit its target of having 6 US clinical sites on board in 1Q 2021. It is truly uplifting to be working on the details of getting patients enrolled and treated at these sites. Theralase is another step closer in achieving its next milestone of enrolling and treating 9 additional patients in early 2021 to meet the target of 25 patients for potential Breakthrough Designation."

Japan’s Ministry of Health, Labour and Welfare Approves Breyanzi, a New CAR T Cell Therapy

On March 25, 2021 Bristol Myers Squibb K.K. reported that Japan’s Ministry of Health, Labour and Welfare (MHLW) approved Breyanzi (lisocabtagene maraleucel: liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma1 and R/R follicular lymphoma (Press release, Bristol-Myers Squibb, MAR 25, 2021, View Source [SID1234577148]).2

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The approval is based on efficacy and safety from the TRANSCEND NHL 001 trial in patients with R/R B-cell non-Hodgkin lymphoma (NHL) and the TRANSCEND WORLD trial in patients with R/R aggressive B-cell NHL.

Large B-cell lymphoma comprises several disease types including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common form of non-Hodgkin lymphoma in Japan, accounting for 30-40% of all B-cell cases diagnosed,3 and is especially prevalent among people in their 60’s.4 There is currently no established standard-of-care treatment for patients with R/R large B-cell lymphoma,5 which underscores the need for new treatments for in this disease area. Follicular lymphoma accounts for 10-20% of all B-cell NHL cases in Japan. Patients initially respond to chemotherapy, but relapse is common, especially in advanced-stage patients.5 There is also no established standard-of-care treatment for patients with follicular lymphoma grade 3B.5

Jean-Christophe Barland, President and CEO of Bristol-Myers Squibb K.K. and Celgene K.K., said, "I am pleased that we have received regulatory approval in Japan for Breyanzi, our first CAR T cell therapy, which will allow us to provide a new treatment option for patients fighting relapsed or refractory large B-cell lymphoma and relapsed or refractory follicular lymphoma. In addition, we are filing an application for a further CAR T cell therapy to address more unmet medical needs. As a game-changer committed to ‘innovation with heart’, Bristol Myers Squibb will continue on its journey to help patients prevail over serious diseases."

Breyanzi is a chimeric antigen receptor T cell therapy designed to target CD19, which is expressed on the cell during normal B-cell development and maintained even after malignant transformation of B cells. Breyanzi aims to target CD19-expressing cells and is administered in a one-time infusion as a defined, purified composition to reduce variability of the CD8 and CD4 component dose. Breyanzi will be manufactured at Bristol Myers Squibb’s cellular immunotherapy manufacturing facility in Bothell, Washington and at a partner company facility in Japan.

Breyanzi was approved by the U.S. Food and Drug Administration on February 5, 2021 for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma. Breyanzi has been granted Priority Medicines (PRIME) designation for relapsed or refractory DLBCL in the European Union and a Marketing Authorization Application is currently under review by the European Medicines Agency.

TRANSCEND NHL 001 / TRANSCEND WORLD Trial Key Results

In the TRANSCEND NHL 001 trial, of 133 subjects in the primary efficacy evaluation population, the overall response rate [95% CI], which was the primary endpoint, was 74.4% [66.2, 81.6] (April 12, 2019 data cutoff), and the lower limit of the 95% CI therefore exceeded the protocol-defined threshold overall response rate of 40%. In addition, the overall response rate [95% CI] in the 256 subjects in the efficacy analysis population treated with anti-CD19 CAR T cells was 72.7% [66.8, 78.0] (August 12, 2019 data cutoff). In the TRANSCEND WORLD trial, of 34 subjects who received BREYANZI, the overall response rate [95% CI], which was the primary endpoint, was 58.8% [40.7, 75.4] (September 13, 2019 data cutoff), which was statistically significant compared to the threshold value of 40%. In addition, the overall response rate [95% CI] in the 10 Japanese subjects was 70.0% [34.8, 93.3]. Moreover, the overall response rates [95% CIs] in the 46 subjects in the study population overall and in the 10 Japanese subjects at the June 19, 2020 data cutoff were 63.0% [47.5, 76.8] and 70.0% [34.8, 93.3], respectively.

In the TRANSCEND NHL 001 trial, 269 patients treated with Breyanzi were evaluated for safety. Adverse reactions occurred in 201 patients including cytokine release syndrome (42.0%), fatigue (17.8%), neutropenia (16.4%), anemia (13.8%), headache (13.4%), thrombocytopenia (11.5%), confusion (11.5%), tremor (11.2%), and hypotension (10.4%) (aggregated until approval). Adverse reactions occurred in 42 patients out of 46 (including 10 Japanese) treated with Breyanzi in the TRANSCEND WORLD trial. Adverse reactions included neutropenia (52.2%), cytokine releasesyndrome (41.3%), anemia (39.1%), thrombocytopenia (39.1%), pyrexia (39.1%), leukopenia (23.9%), confusion (15.2%), fatigue (13.0%), and febrile neutropenia (13.0%) (aggregated until approval).

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

Phio Pharmaceuticals Reports 2020 Year End Financial Results and Provides Business Update

On March 25, 2021 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported its financial results for the year ended December 31, 2020 and provided a business update (Press release, Phio Pharmaceuticals, MAR 25, 2021, View Source [SID1234577147]).

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"Over the past year, we established steady momentum across our development programs and expanded our pipeline, including our new collaboration with AgonOx, Inc. to develop T cell-based cancer immunotherapies using PH-762. This progress has resulted in a steady stream of preclinical data, which we plan to present for several programs throughout 2021. Also, we are on track to initiate two clinical studies for our lead asset, PH-762, later this year," said Dr. Gerrit Dispersyn, President and CEO of Phio. "In support of the planned initiation of two clinical programs for different applications of PH-762, and of the advancement of our broader development pipeline, we recently completed two equity financings for additional gross proceeds of $21.7 million. Our stronger financial footing is expected to fund our current programs for the next two years, including clinical studies on the safety and efficacy of PH-762 in adoptive cell therapy and with direct drug therapy."

Quarter in Review and Recent Corporate Updates

Presented data at SITC (Free SITC Whitepaper) 2020 showing that the antitumoral efficacy of our PH-762, PH-790 and PH-804 INTASYL compounds can be further improved by combining them in a single drug treatment.
Presented data resulting from our collaborations with AgonOx, Inc. and the Helmholtz Zentrum München, including poster presentations at SITC (Free SITC Whitepaper) 2020.
Announced a collaboration for the clinical development of novel T cell-based cancer immunotherapies using PH-762 and AgonOx, Inc.’s "double positive" (DP) tumor-infiltrating lymphocyte (TIL) technology. Data developed in collaboration with AgonOx, Inc. showed PH-762 can improve the tumor cell killing activity of DP TILs two-fold.
Bolstered the balance sheet with two financings in Q1 2021 for gross proceeds of $21.7 million in additional capital.
Completed a $7.7 million registered direct offering of common stock priced at-the-market.
Completed a $14.0 million private placement of common stock and warrants priced at-the-market.
Upcoming Pipeline Milestones for 2021

Scheduled to present new study data regarding direct drug therapy with PH-762 at the AACR (Free AACR Whitepaper) Annual Meeting 2021.
Additional data publications on the Company’s pipeline programs, expected during Q2-Q3 2021.
Start of a first-in-human clinical study, on the use of PH-762 in adoptive cell therapy with TILs, namely, to enhance the therapeutic responses in cancer patients. The study, to be executed in collaboration with Agonox, Inc., is expected to be initiated in Q3 2021.
Start of a first-in-human clinical study on the use of PH-762 as directly administered drug in patients with advanced melanoma. The study is expected to be initiated in Q4 2021.
Financial Results

Cash Position

At December 31, 2020, the Company had cash of $14.2 million as compared with $6.9 million at December 31, 2019. Subsequent to the end of the fourth quarter of 2020, the Company raised an additional $21.7 million in gross proceeds through a registered direct offering and a private placement offering. The Company expects its current cash will be sufficient to fund currently planned operations to the second quarter of 2023.

Research and Development Expenses

Research and development expenses were approximately $4.4 million for the year ended December 31, 2020, compared to approximately $4.3 million for the year ended December 31, 2019. The increase is primarily due to an increase in the use of sponsored research organizations to support the development of the Company’s pipeline programs as compared to the prior year period.

General and Administrative Expenses

General and administrative expenses were approximately $4.4 million for the year ended December 31, 2020, compared to approximately $4.7 million for the year ended December 31, 2019. The decrease is primarily due to decreases in legal-related expenses and recruiting fees to support employee hiring activities as compared to the prior year period.

Net Loss

Net loss was $8.8 million, or $1.92 per share, for the year ended December 31, 2020, compared with $8.9 million, or $19.33 per share, for the year ended December 31, 2019. The decrease in net loss was primarily attributable to the decrease in general and administrative expenses, as described above. The change in net loss per share was primarily due to an increase in the number of shares outstanding as a result of our capital raise activities as compared to the prior year period.

Neoleukin Therapeutics Announces Year End 2020 Financial Results

On March 25, 2021 Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, reported a corporate update and financial results for the year ended December 31, 2020 (Press release, Neoleukin Therapeutics, MAR 25, 2021, View Source [SID1234577146]).

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"Despite the challenges of the COVID-19 pandemic, our team has remained focused and committed to the advancement of our de novo technology platform, paving the way for future achievements this year and beyond," said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. "In 2021, we look forward to advancing our first-in-human trials of NL-201 and expanding our de novo protein technology and pipeline."

Recent Updates

NL-201 Development

NL-201 is a computationally designed de novo protein that is a mimetic of natural cytokines IL-2 and IL-15. In the fourth quarter of 2020, Neoleukin submitted a Clinical Trial Notification ("CTN") for Phase 1 clinical testing of NL-201 in Australia, which is anticipated to be initiated at leading clinical research centers in the first half of 2021. In addition, in December 2020, Neoleukin announced submission of an Investigational New Drug ("IND") Application with the U.S. Food and Drug Administration ("FDA") to begin Phase 1 clinical testing of NL-201 in the U.S. The planned clinical trial of NL-201 in Australia and North America is expected to enroll patients with relapsed or refractory solid tumors. Patients will receive NL-201 as intravenous monotherapy to assess safety, pharmacokinetics, pharmacodynamics, and antitumor activity.

On January 7, 2021, Neoleukin received a clinical hold letter from the FDA related to its IND Application. The FDA requested that the company develop a new assay for methods-of-use testing and to demonstrate that this assay can more precisely measure the amount of NL-201 that is delivered to the patient when following the pharmacy preparation and administration instructions. The FDA also had additional requests not related to the clinical hold to be addressed by amendment of the IND. Neoleukin is working to address the FDA’s questions as quickly as possible and currently expects to resolve the clinical hold as well as to begin enrollment of patients in the first half of 2021.

In addition to the systemic trial, Neoleukin is planning a trial of NL-201 to test local administration in order to achieve higher drug concentrations in the tumor microenvironment. The company expects the local administration trial to begin by the end of 2021 and will provide further details as appropriate.

In November 2020, Neoleukin presented preclinical data on NL-201 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 35TH Anniversary Annual Meeting. These data highlighted the results of multiple experiments of NL-201 in combination with immunotherapies and demonstrate that NL-201 enhances activity of checkpoint inhibitors and tumor-targeting antibodies in preclinical models.

De Novo Protein Design for Coronavirus – NL-CVX1

In November 2020, Neoleukin announced publication in the journal Science of a manuscript describing novel molecules designed to treat or prevent infection by SARS-CoV-2, the virus that causes COVID-19. As reported, the optimized proteins act as decoys that bind to the SARS-CoV-2 spike protein with high affinity, preventing its association with the viral receptor hACE2 and blocking cellular entry. The lead molecule, NL-CVX1 (CTC-445.2d), was shown to prevent infection of multiple cell lines in vitro and, when administered intranasally, to prevent serious consequences of SARS-CoV-2 infection in hamsters. The rapid development of this targeted protein demonstrates the potential of the Neoleukin de novo protein design platform. Neoleukin is currently planning a first-in-human trial of NL-CVX1, and will continue to evaluate the program as the SARS-CoV-2 landscape evolves.

Other Research Updates

Neoleukin has multiple research projects underway evaluating the applications of de novo protein technology to develop agonists and antagonists of immune pathways. This includes development of potent and hyperstable inhibitors of inflammation that could be used to treat autoimmune conditions. Neoleukin currently plans to announce additional information about its pipeline program during the second half of 2021.

Summary of Financial Results

Cash Position: Cash and cash equivalents totaled $192.6 million as of December 31, 2020, compared to $143.1 million as of December 31, 2019. The increase was primarily driven by the completion of a public offering in July 2020 for net proceeds of $71.3 million. Based upon current internal infrastructure and pipeline initiatives, Neoleukin believes it has sufficient cash to fund operations into 2023.

R&D Expenses: Research and development expenses for the year ended December 31, 2020 were $24.3 million compared to $4.4 million for the year ended December 31, 2019. The increase in research and development expenses during the year ended December 31, 2020 was due to increased expenses incurred from IND-enabling activities related to our lead product candidate, NL-201, and in connection with the advancement of other Neoleukin technologies. Lower research and development costs during the year ended December 31, 2019 reflect the fact that prior to the merger between Aquinox Pharmaceuticals, Inc. ("Aquinox") and Neoleukin Therapeutics, Inc. ("Former Neoleukin") in August, 2019, all research and development activities with rosiptor had been suspended since June 2018.

G&A Expenses: General and administrative expenses for the year ended December 31, 2020 were $17.2 million compared to $18.8 million for the year ended December 31, 2019. The higher general and administrative expenses for the year ended December 31, 2019 as compared to the year ended December 31, 2020 were primarily due to severance costs and the recognition of stock-based compensation expense for certain options that vested as a result of the merger between Aquinox and Former Neoleukin in August 2019. The general and administrative expenses for the year ended December 31, 2020 reflect an increase in personnel related costs, facility-related costs, and professional service fees.

Acquired in-process R&D: The acquired in-process research and development expense of $47.7 million in 2019 arose from the merger between Aquinox and Former Neoleukin in 2019 and was expensed immediately in accordance with accounting standards.

Gain on Sale of Aquinox Canada: The gain relates to the sale of Aquinox Canada, a wholly owned subsidiary of the company, during the three months ended September 30, 2020. The gain of $7.8 million recognized is the total consideration of $8.2 million, less transaction costs of $0.4 million.

Net Loss: Net loss for the year ended December 31, 2020 was $33.3 million compared to a net loss of $69.4 million for the year ended December 31, 2019. The higher net loss in 2019 is primarily due to the acquired in-process research and development expense from the merger.

Conference Call Information

Neoleukin will host a conference call today to discuss 2020 financial results and provide a corporate update. Details as follows:

The archived audio webcast will be available on the Investor Relations section of the Neoleukin website approximately two hours after the event and will be available for replay for at least 30 days after the event.

About NL-201

NL-201 is a de novo receptor agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the alpha receptor subunit (CD25). Previously presented preclinical data have demonstrated the ability of NL-201 to stimulate and expand CD8+ and NK cells at low doses with minimal impact on immunosuppressive regulatory T cells.

Relay Therapeutics Reports Fourth Quarter and Full Year 2020 Financial Results and Operational Highlights

On March 25, 2021 Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading edge experimental and computational technologies, reported fourth quarter and full year 2020 financial results and operational highlights (Press release, Relay Therapeutics, MAR 25, 2021, View Source [SID1234577145]).

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"2020 was a transformational year for Relay Therapeutics. We successfully advanced multiple programs into the clinic, evolved our platform, expanded our strong team and completed a successful IPO," said Sanjiv Patel, M.D., president and chief executive officer. "While the last few years were spent validating our approach of combining leading edge experimental and computational techniques to create potentially life-saving therapies for patients, the next chapter will be about extending our platform leadership and delivering meaningful clinical results to support the success of our programs. 2021 will be a critical year of execution as we advance our mission of transforming drug discovery to address some of the most devastating diseases."

2020 Corporate Highlights

Initiated first-in-human clinical studies for RLY-1971 (SHP2 inhibitor) and RLY-4008 (FGFR2 inhibitor)
Progressed PI3Kα mutant selective program into late lead optimization
Continued to advance three additional precision oncology programs through preclinical development
Expanded research efforts into genetic diseases with two preclinical programs
Strengthened the balance sheet with $460 million gross proceeds raised in an initial public offering
Announced a worldwide license and collaboration agreement with Genentech, Inc., a member of the Roche Group, for the development and commercialization of RLY-1971
2021 Anticipated Milestones

Present preclinical data for RLY-4008 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021
Announce initial clinical data for RLY-4008 in the second half of 2021
Genentech to initiate RLY-1971 and GDC-6036 (KRAS G12C inhibitor) combination trial
Enter IND-enabling studies for PI3Kα mutant selective inhibitor and provide program update
Fourth Quarter and Full Year 2020 Financial Results

Cash, Cash Equivalents and Investments: As of December 31, 2020, cash, cash equivalents and investments totaled approximately $678.1 million, compared to $355.8 million as of December 31, 2019. The Company expects its current cash and cash equivalents, including the $75 million upfront payment received from Genentech in 2021, will be sufficient to fund its current operating plan into 2024.

R&D Expenses: Research and development expenses were $32.1 million for the fourth quarter of 2020, as compared to $22.4 million for the fourth quarter of 2019. This increase was primarily due to $7.4 million of increased employee related costs, including $5.7 million of additional share-based compensation expense, primarily due to increases in our stock price and increased headcount, and $2.3 million in increased clinical trial expenses. Research and development expenses were $99.9 million for the full year 2020, as compared to $70.3 million for the full year 2019.

G&A Expenses: General and administrative expenses were $15.5 million for the fourth quarter of 2020, as compared to $3.4 million for the fourth quarter of 2019. This increase was primarily due to $9.1 million of increased employee related costs, including $7.5 million of additional share-based compensation expense, primarily due to increases in our stock price and increased headcount, as well as $3.0 million of increased general expenses, primarily driven by public company related costs. General and administrative expenses were $38.6 million for the full year 2020, as compared to $13.7 million for the full year 2019.

Net Income/Loss: Net income was $35.3 million for the fourth quarter of 2020, as compared to a net loss of $23.9 million for the fourth quarter of 2019. Net loss was $52.4 million for the full year 2020, or a net loss per share of $5.40, as compared to a net loss of $75.3 million for the full year 2019, or a net loss per share of $21.82.