On August 13, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that the U.S. Food and Drug Administration (FDA) has accepted the Company’s New Drug Application (NDA) for umbralisib, the Company’s investigational once-daily, oral, dual inhibitor of PI3K-delta and CK1-epsilon, as a treatment for patients with previously treated marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 based regimen and follicular lymphoma (FL) who have received at least two prior systemic therapies (Press release, TG Therapeutics, AUG 13, 2020, View Source [SID1234563567]). The MZL indication, under Breakthrough Therapy Designation (BTD), has been accepted for Priority Review and has a Prescription Drug User Fee Act (PDUFA) goal date of February 15, 2021. The FL indication has been accepted for standard review with a PDUFA goal date of June 15, 2021. The FDA also notified the Company that it is not currently planning to hold an advisory committee meeting to discuss this application.

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Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "We are extremely pleased with the FDA’s acceptance of our first NDA submission and look forward to working with the FDA during the review process. This is a significant achievement in our path towards accomplishing our goal of developing novel treatments for patients with B-cell diseases." Mr. Weiss continued, "If approved, we believe umbralisib could become an important treatment option for patients with previously treated MZL and FL. We look forward to presenting the data from the UNITY-NHL trial that supported this NDA submission by year end."

The NDA for umbralisib was based primarily on data from the umbralisib monotherapy MZL and FL cohorts of the UNITY-NHL Phase 2b trial evaluating patients with relapsed/refractory MZL or FL. The Company has previously announced that each cohort met its primary endpoint of overall response rate (ORR), meeting the Company’s target guidance of 40-50% ORR, as confirmed by an Independent Review Committee (IRC). The FDA has also previously granted umbralisib Breakthrough Therapy Designation (BTD) for MZL and orphan drug designation (ODD) for MZL and FL.

ABOUT THE UNITY-NHL PHASE 2b STUDY—MZL & FL COHORTS
The UNITY- NHL trial is a global multicenter, open-label Phase 2b trial.

The MZL cohort was designed to evaluate the safety and efficacy of single agent umbralisib in patients with MZL who have received at least one prior anti-CD20 regimen. In February of 2019, the Company announced that the primary endpoint of overall response rate (ORR) as determined by Independent Review Committee (IRC) was met for all treated MZL patients. The results met the Company’s target guidance of 40-50% ORR. Interim safety and efficacy data from the MZL cohort were presented in oral presentations in 2019 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and the International Conference on Malignant Lymphoma (ICML).

The FL cohort was designed to evaluate the safety and efficacy of single agent umbralisib in patients with FL who were relapsed or refractory following at least two prior lines of therapy, including an anti-CD20 regimen and an alkylating agent. In October of 2019, the Company announced that the primary endpoint of ORR as determined by IRC was met for all treated FL patients. The results met the Company’s prespecified response target of 40-50% ORR.

On June 15, 2020, the Company announced the completion of the rolling submission of a NDA to the FDA requesting accelerated approval of umbralisib as a treatment for patients with previously treated MZL and FL.

On August 12, 2020, the Company received notification from the FDA of its acceptance of the Company’s NDA for umbralisib as a treatment for patients with previously treated MZL and FL.

ABOUT MARGINAL ZONE LYMPHOMA
Marginal zone lymphoma (MZL) comprises a group of indolent (slow growing) mature B-cell non-Hodgkin lymphomas (NHLs). MZL is generally considered a chronic and incurable disease. With an annual incidence of approximately 7,500 newly diagnosed patients in the United States1, MZL is the third most common B-cell NHL, accounting for approximately eight percent of all NHL cases. MZL consists of three different subtypes: extranodal MZL of the mucosal-associated lymphoid tissue (MALT), nodal marginal zone lymphoma (NMZL), and splenic marginal zone lymphoma (SMZL)2.

ABOUT FOLLICULAR LYMPHOMA
Follicular lymphoma (FL) is typically an indolent form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes. It is the second most common form of NHL. FL is generally not curable and is considered a chronic disease, as patients can live for many years with this form of lymphoma. With an annual incidence in the United States of approximately 15,000 newly diagnosed patients3, FL is the most common indolent lymphoma accounting for approximately 20 percent of all NHL cases4.

On August 13, 2020 ProMIS Neurosciences, Inc. (TSX: PMN) (OTCQB: ARFXF) ("ProMIS or the Company"), a biotechnology company focused on the discovery and development of antibody therapeutics targeting toxic oligomers implicated in the development of neurodegenerative diseases, reported its operational and financial results for the three and six months ended June 30, 2020 (Press release, ProMIS Neurosciences, AUG 13, 2020, View Source [SID1234563557]).

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"Over the course of the second quarter of 2020, the value of our unique discovery and development platform was further evidenced as ProMIS made considerable progress in expanding its portfolio of opportunities across multiple neurodegenerative diseases and also in initiated two new diagnostic

programs." stated Eugene Williams, ProMIS’ Executive Chairman. "We look forward to continued progress applying our unique technology platform to the development of disease-modifying antibody therapies, diagnostics and potential vaccines for Alzheimer’s disease, as well as the development of highly accurate assays for detection of antibodies against the virus causing COVID-19."

Corporate Highlights

In April and May 2020, the Company received gross proceed of $1,239,195 from the exercise of 9,532,276 warrants from the warrant repricing program announced in March 2020. The exercise price of the Warrants was repriced to $0.13 per share, effective April 8, 2020 until May 22, 2020 (Warrant Repricing Period). At the end of the Warrant Repricing Period, the Warrants reverted to the original exercise price. All other terms of the Warrants remain unchanged.
On April 7, 2020, we announced that the Alzheimer’s Association International Conference (AAIC) had accepted several abstracts for our Alzheimer’s disease (AD) program. The AAIC also invited ProMIS’ Chief Development Officer, Dr. Johanne Kaplan, to chair a session on novel immunotherapeutic approaches for the treatment of AD.
On April 9, 2020, we announced that the journal Neurology would publish abstracts of data demonstrating the strength of ProMIS’ antibody programs targeting toxic forms of alpha-synuclein in Parkinson’s disease (PD) and toxic forms of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS). The data appeared in the April 14, 2020 online supplement to Neurology, the most widely read, highly cited peer-reviewed neurology journal.
On April 30, 2020, we announced we had generated intrabodies highly selective for misfolded forms of TDP-43 implicated in ALS, frontotemporal dementia (FTD) and several other neurologic disorders. Early data support the use of these intrabodies within gene therapy vectors based on their selectivity and ability to promote degradation of toxic species of TDP-43 while preserving normal forms of the protein.
On May 6, 2020, we announced the identification of novel antagonists against the receptor for activated protein kinase C1(RACK1) that prevent the formation of dysfunctional protein aggregates and act to restore normal function. Evidence indicates that targeting RACK1 is a promising new strategy to address the complex mechanisms involved in the pathogenesis of neurodegenerative diseases, including ALS.
On May 12, 2020, the Company announced its program to develop a high-throughput, highly accurate test for detection of antibodies to SARS CoV-2, the causative agent of COVID-19. ProMIS has identified 18 potential antibody targets unique to the spike protein halo of SARS CoV-2.
On May 19, 2020, we announced that, in addition to its ongoing program to develop a high-throughput and accurate test for detection of antibodies to the causative agent of COVID-19, it has expanded its collaboration with BC Neuroimmunology (BCNI) to include development of highly sensitive and specific assays to support accurate screening and diagnosis of AD.
On May 28, 2020, together with a team of commercial and academic collaborators, we shared a Digital Technology Supercluster award from the Government of Canada for 1.8 million Canadian dollars. The project, "Predicting the evolution of COVID-19," brings together six commercial and academic collaborators to predict likely mutations of SARS-CoV-2. The findings will inform the early design of effective tests, therapies and vaccines, allowing public health systems globally to prepare and ideally prevent future pandemics caused by evolving strains of the virus.
On June 17, 2020 the Company and BCNI announced significant progress on development of a highly accurate antibody test for COVID-19. The serology test achieves 99.9% sensitivity and 99.5% specificity for SARS CoV-2. ProMIS’ proprietary peptide antigens are currently under evaluation for their potential ability to detect neutralizing antibodies in the next phase of assay development.
On June 24, 2020, the Board of Directors, having considered current COVID-19 public health restrictions, determined it to be in the best interests of the company and its shareholders to adjourn the company’s annual meeting of shareholders ("AGM") to 9:00 a.m. (Pacific Time) on July 29, 2020 and to change the location of the AGM to Suite 1500, 1055 West Georgia Street, Vancouver, British Columbia.
Financial Results

Results of Operations – Three months ended June 30, 2020 and 2019

The Company’s net loss for the three months ended June 30, 2020 was $1,650,218, compared to a net loss of $1,858,530 for the three months ended June 30, 2019. Included in the net loss amount for the three months ended June 30, 2020 were non-cash expenses of $76,310, representing share-based compensation and amortization of an intangible asset, compared to $153,461 for the three months ended June 30, 2019. The decrease in the net loss for the three months ended June 30, 2020 reflects decreased costs associated with external contract research organizations for internal programs, decreased consulting and professional fees and share-based compensation offset by increased patent expense and foreign exchange losses.

Research and development expenses for the three months ended June 30, 2020 were $898,887, as compared to $1,042,618 in the three months ended June 30, 2020. The decrease in research and development expense for the three months ended June 30, 2020, is primarily attributed to decreased costs associated with external contract research organizations for internal programs and share-based compensation offset by increased patent expense.

General and administrative expenses for the three months ended June 30, 2020 were $752,896, as compared to $815,937 in the three months ended June 30, 2019. The decrease for the three months ended June 30, 2020, compared to the same period in 2019, is primarily attributable to a reduction in consulting and professional fees offset by increased foreign exchange losses.

Results of Operations – Six months ended June 30, 2020 and 2019

The Company’s net loss for the six months ended June 30, 2020 was $3,412,137, compared to a net loss of $4,305,107 for the six months ended June 30, 2019. Included in the net loss amount for the six months ended June 30, 2020 were non-cash expenses of $290,048, representing share-based compensation, warrant modification and amortization of an intangible asset, compared to $417,334 for the six months ended June 30, 2019. The decrease in the net loss for the six months ended June 30, 2020 reflects decreased costs associated with external contract research organizations for internal programs, patent costs, decreased consultant salaries and associated costs and share-based compensation offset by foreign exchange losses.

Research and development expenses for the six months ended June 30, 2020 were $1,874,473, as compared to $2,813,271 in the six months ended June 30, 2019. The decrease in the research and development expenses for the six months ended June 30, 2020, is primarily attributed to decreased costs associated with external contract research organizations for internal programs, patent costs, decreased consultant salaries and associated costs and share-based compensation offset by increased consulting expense.

General and administrative expenses for the six months ended June 30, 2020 were $1,541,242, as compared to $1,491,861 in the six months ended June 30, 2019. The increase for the six months ended June 30, 2020, compared to the same period in 2019, is primarily attributable to warrant modification expense and increased foreign exchange losses offset by a reduction in consulting and professional fees.

Outlook

As a prelude to the first PMN310 clinical trial in AD, we plan on using a novel biomarker approach that may show evidence of slowing of neuronal death as early as Phase 1 in the anticipated clinical development program. Furthermore, as the ability to achieve early detection of AD develops, based on the advent of reliable blood-based biomarkers for AD detection, the need for preventive treatment will grow. Therapeutic vaccines can be used for that purpose. Using our discovery platform, our aim is to devise a safe and effective AD vaccine to induce a specific immune response against toxic oligomers of amyloid beta.

The Company will also continue to further characterize the potential benefits of its programs selectively targeting toxic aggregates of TDP-43 in ALS, toxic forms of alpha-synuclein in PD and toxic aggregates of tau in AD and other dementias. Our unique platform produces antibodies that meet a key success factor for the development of therapeutics and vaccines for neurodegenerative diseases: the ability to selectively target the neurotoxic form of a protein implicated as a root cause of disease, while sparing the normal forms of the protein.

In the infectious disease setting, we will focus our unique technology platform to identify peptide antigens that can be used as an essential component to create accurate and sensitive serological assays to detect the presence of potentially neutralizing antibodies that arise in response to a specific infection, such as COVID-19.

On August 13, 2020 Isofol Medical AB (publ) ("Isofol"), (Nasdaq First North Premier Growth Market: ISOFOL) reported that it entered into a license agreement with Solasia Pharma K.K ("Solasia") (TSE: 4597), a specialized oncology company headquartered in Japan, to develop and commercialize Isofol’s proprietary late-stage drug candidate arfolitixorin in Japan (Press release, Isofol Medical, AUG 13, 2020, View Source [SID1234563556]). Under the terms of the agreement, Isofol will receive a total amount of ~$ 100 million* (SEK 890 million*) as upfront, development, regulatory and sales-based milestone payments and clinical development cost. In addition, Isofol will receive tiered royalties on net sales in solid double digit figures.

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The license agreement is initially focused on the development and commercialization of arfolitixorin as first-line treatment for metastatic colorectal cancer (mCRC) patients in Japan, which is projected to be the second largest addressable patient market for arfolitixorin. Additional indications will be evaluated jointly by Solasia and Isofol. Isofol retains rights to arfolitixorin in the rest of the world.

"This agreement represents an important next step for the development and commercialization of arfolitixorin. This is Isofol’s biggest milestone yet in the development process of our proprietary drug candidate and a strong validation from a specialized innovative oncology partner in the local Japanese market. Solasia’s proven capabilities to develop and commercialize oncology treatments in Japan and other Asian markets as well as their commitment to cancer patients make them the ideal partner to support our development and commercialization efforts in Japan," said Ulf Jungnelius, M.D, CEO of Isofol.

Isofol will remain as global sponsor of the AGENT study and Solasia will supervise clinical development activities in Japan and be responsible for registrational filing, and following potential regulatory approvals, Solasia will, as the Market Authorization holder, be responsible for the commercialization of arfolitixorin in Japan. Furthermore, Solasia will pay solid double digit tiered royalty rates on future net sales applicable for the deal.

"Arfolitixorin is an important addition to our expanding portfolio of innovative oncology therapies. Japan is the second largest market for arfolitixorin with more than 150,000** people diagnosed with CRC annually. We look forward to working collaboratively with Isofol to accelerate our goal of bringing a new treatment option to patients living with mCRC in Japan," said Yoshihiro Arai, President & CEO of Solasia.
Isofol’s drug candidate arfolitixorin is being evaluated in the ongoing global Phase 3 AGENT study, as a first-line treatment for mCRC. The study is currently being conducted in the U.S., Canada, Europe, Australia and Japan. On February 18, Isofol announced that the first patient in Japan had initiated treatment in the AGENT study. Isofol together with Solasia plans to expand the study with additional sites in Japan, in addition to the 90 clinics that are already open worldwide.

* The total value of upfront, development, regulatory, sales-based milestone payments and clinical development cost is up to JPY 10.4 billion. The amount given in USD and SEK is subject to exchange rate.

** Source: Center for Cancer Control and Information Services, National Cancer Center

Isofol was advised on the transaction by Shadow Lake Group Inc., and the Setterwalls lawfirm.

Invitation to a conference call and webcast on August 13, 2020 at 11:00 (CEST)
Isofol invites investors, analysts and media to a conference call in connection with the licensing agreement with Solasia. The presentation will be held by CEO Ulf Jungnelius in English and will conclude with a Q&A session. Questions can be asked on the telephone conference or in written form through the webcast. No preregistration is needed.

This information is information that Isofol Medical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 08:30 CEST on August 13, 2020.

On August 12, 2020 Xspray Pharma AB (publ) (Nasdaq Stockholm: XSPRAY) reported preliminary data from the first out of two bioequivalence studies in healthy volunteers with its lead product candidate HyNap-Dasa (Press release, Xspray, AUG 12, 2020, View Source [SID1234649570]). The primary aim was to demonstrate bioequivalence for HyNap-Dasa compared to the reference product Sprycel. The first study did not fulfil statistical bioequivalence requirements due to high variability in pharmacokinetic parameters for the reference product Sprycel. A few subjects had very low absorption from Sprycel which was not observed for HyNap-Dasa. As these data with negligible absorption from Sprycel do not represent a clinically relevant treatment drug exposure, Xspray intends to discuss the results with the FDA before submitting the ANDA application.

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This first pivotal study with HyNap-Dasa was performed in 51 healthy volunteers under fasting conditions over a period of four weeks where each volunteer received two repeated single doses of HyNap-Dasa and Sprycel in a randomized cross-over design. Final results from full data analysis are expected in September. The second bioequivalence study, where the effect of food intake on the absorption is assessed, is ongoing and preliminary results are expected in the end of September. The totality of data from the two clinical studies will form the basis for the coming ANDA application.

"These first data indicate that formal bioequivalence criteria were not met which was mainly related to unusually poor absorption of dasatinib from the Sprycel formulation in a few subjects. We are now waiting for the final study report of this first study, as well as the preliminary data from the second study with food intake which is expected end of September. Both studies will form the basis for the ANDA application. Provided positive response from the FDA, we can still file at the end of the year." says Per Andersson, CEO of Xspray Pharma.

In addition to Xspray’s continued work towards an ANDA application based on the current and the ongoing study, Xspray will in parallel prepare for an additional bioequivalence study as a back-up. The validated manufacturing process enables this study to be initiated within 4 – 6 months.

"Since we have achieved bioequivalence earlier in two smaller studies, the outcome of this study was unexpected. We have analysed the results and have a good understanding of the factors that contributed to this outcome. We are planning to adjust the formulation in case the FDA decides that an additional study is needed. Alongside our efforts of getting the ANDA for HyNap-Dasa approved we are proceeding with the preparation of the next products in our portfolio as planned, an improved version of HyNap-Dasa and HyNap-Nilo, which both will follow the 505(b)(2) regulatory pathway. Furthermore, our planned business development efforts around HyNap-Dasa will progress according to plan," Per Andersson concludes.

An audiocast with the possibility to ask questions on the results is scheduled at 08:00 CEST on August 13 (audiocast will be held in Swedish): View Source 12, 2020

On August 12, 2020 Theralase Technologies Inc. ("Theralase" or "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light activated Photo Dynamic Compounds ("PDC") and associated drug formulations, reported that three out of four of its Canadian clinical study sites have re-commenced new patient enrollment and treatment in the Company’s Phase II Non-Muscle Invasive Bladder Cancer ("NMIBC") clinical study ("Study II") (Press release, Theralase, AUG 12, 2020, View Source [SID1234568619]).

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Specifically:

Study Site Location Site Status
University Health Network ("UHN") Toronto, Ontario Enrolling
London Health Sciences Centre ("LHSC"), London, Ontario Enrolling
Nova Scotia Health Authority ("NSHA") Halifax, Nova Scotia Enrolling
McGill University Health Centre ("MUHC") Montreal, Quebec COVID-19 Hold
On a go forward basis, all future and existing patients to be enrolled and treated (initial and second treatment) in Study II will be treated using the Study II treatment optimizations as communicated via press release on July 30, 2020, specifically:

Bladder volume calculation
Study drug volume calculation
Study device volume calculation
Study device treatment time
Four of the patients previously treated are awaiting second treatment subject to the clinical study site operating room availability. One additional patient is undergoing additional assessments prior to proceeding to second treatment.

The Company is in advanced discussions to launch a number of US based clinical study sites, 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 in 1Q2021.

Shawn Shirazi, Ph.D., Chief Executive Officer of Theralase stated, "Theralase is pleased that 3 out of 4 Canadian clinical study sites are open for new patient enrollment and treatment receiving the new optimized Study II treatment. The clinical data collected on the first twelve patients treated shows a favorable clinical response, which the Company expects will improve due to the implemented Study II treatment optimization."

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 a 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