On August 14, 2018 ProMIS Neurosciences, Inc. (TSX: PMN; OTCQB: ARFXF), 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, 2018 (Press release, ProMIS Neurosciences, AUG 14, 2018, View Source [SID1234528931]).

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"Over the first half of 2018, we focused on three key priorities to advance our business", stated ProMIS Executive Chairman, Eugene Williams. "First, to continue to push toward our goal of initiating the first clinical trial of PMN310 in the second half of 2019; second, to differentiate the oligomer selectivity of PMN310 as best in class profile for the treatment of Alzheimer’s disease (AD) versus other amyloid-beta directed therapies in development; and third, to expand our portfolio by developing therapeutic antibodies targeting toxic oligomers of alpha-synuclein for Parkinson’s disease (PD) and toxic aggregates of Tar-DNA binding protein (TDP43) for ALS. We are pleased to be on target to meet our objectives for the year and look forward to communicating our accomplishments."

Recent Corporate Highlights

On May 1, we announced completion of a private placement of 19,306,668 common share units at a price of $0.375 per unit, for gross proceeds of approximately $7,240,000. Each unit consisted of one common share and one-half of a common share purchase warrant. Each whole warrant is exercisable into one common share at a price of $0.48 per share for a 60-month exercise period, subject to earlier expiry on 30 days’ notice if, at any time after four months from closing, the 20-day volume-weighted average trading price of the Company’s common shares is greater than CDN$1.00. Net proceeds from the private placement will be used for working capital and general corporate purposes.
During the second quarter of 2018, we received proceeds of $1,550,204 related to the exercise of common stock warrants and stock options. The warrants were exercisable at $0.17, $0.20 and $0.30.
On April 10, we announced publication of a peer reviewed scientific paper describing a novel target on toxic oligomers of amyloid-beta in AD.
On June 12, we announced the initiation of producer cell line development for PMN310, our lead therapeutic antibody candidate for treatment of AD. Selexis, SA will carry out this critical first step in the manufacturing of antibody therapeutics using their proprietary Selexis SUREtechnology Platform.
On June 26, we announced that our unique discovery platform generated potential new antibody therapeutic candidates targeting toxic oligomers implicated in the development and progression of PD and ALS.
On June 28, we announced results of the Annual Meeting of Shareholders, whereby all of the resolutions announced in the Management Proxy Circular and placed before the Meeting were overwhelmingly approved by the shareholders.
Financial Results

Results of Operations – Three months ended June 30, 2018 and 2017

The net loss for the three months ended June 30, 2018 was $2,214,861, compared to a net loss of $1,903,396 for the three months ended June 30, 2017. The increased loss in the current period reflects the costs associated with operating the Company’s AD therapeutics program, increased contract research and consultant salaries and associated costs, supporting its patent portfolio and general corporate expenditures.

Research and development expenses for the three months ended June 30, 2018 were $1,531,075, as compared to $1,132,258 in the three months ended June 30, 2017. Costs were higher in the current period due to higher research program costs for the AD therapeutics program, recruiting expenses and higher costs to support its patent portfolio, offset by lower stock-based compensation.

General and administrative expenses for the three months ended June 30, 2018 were $683,786, as compared to $768,696 in the three months ended June 30, 2017. The decreased in expenditures in the current period reflect reduced investor relations expenses and foreign exchange expense, offset by higher consultant salaries and associated costs, other professional fees, and stock-based compensation.

Results of Operations – Six months ended June 30, 2018 and 2017

The net loss for the six months ended June 30, 2018 was $3,771,733, compared to a net loss of $3,275,599 for the six months ended June 30, 2017. The increased loss in the current period reflects the costs associated with operating the Company’s AD therapeutics program, increased contracted research and consultant salaries and associated costs, supporting its patent portfolio and general corporate expenditures.

Revenues for the six months ended June 30, 2018 and 2017 were nominal and relate to legacy technologies.

Research and development expenses for the six months ended June 30, 2018 were $2,229,082, as compared to $1,851,360 in the six months ended June 30, 2017. Costs are higher in the current period due to higher research program costs for the AD therapeutics program, recruiting expenses and higher costs to support its patent portfolio, offset by lower stock-based compensation.

General and administrative expenses for the six months ended June 30, 2018 were $1,542,656, as compared to $1,420,056 in the six months ended June 30, 2017. The increased expenditures in the current period reflect increased consultant salaries and associated costs and higher stock-based compensation, offset by foreign exchange gains.

Outlook

The Company plans to further advance its AD portfolio, with a focus on development of PMN310 for clinical trial initiation in the second half of 2019. Based on the highly selective binding of PMN310 to the toxic Aβ oligomers and lack of off-target binding to non-toxic forms of Aβ (monomer, plaque), the ProMIS AD program will continue to develop data further supporting potential best in class safety and efficacy versus other Aβ-directed therapies currently in development.

Finally, using its unique technology platform, we will advance work to identify and validate selective antibody therapies for the toxic oligomers of alpha synuclein in PD and TDP43 in ALS, with a view to partnering these assets.

On August 13, 2018 ArQule, Inc. (Nasdaq:ARQL), reported the publication of preclinical study data for ARQ 531, the Company’s rationally-designed, reversible inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK) (Press release, ArQule, AUG 13, 2018, View Source [SID1234532694]). The studies, published in Cancer Discovery, were conducted in collaboration with researchers at The Ohio State University. Data from these studies demonstrated efficacy in in vitro and in vivo hematologic malignancy models that recapitulate the most common mechanisms of resistance to irreversible BTK inhibitors, including ibrutinib.

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Highlights from the manuscript (link here) include:

Differentiated Crystal Structure and Biochemical Profile

The crystal structure of ARQ 531 bound to BTK elucidates the mechanism of BTK inhibition that is not dependent on the specific amino acid residue at position 481 (eg. C or S)
Recombinant BTK biochemical assays of ARQ 531 and ibrutinib show similar inhibition for wild type BTK, however ibrutinib has dramatically lower inhibition, binding affinity and residence time for mutant BTK
"Relapsed and refractory patients that develop resistance to ibrutinib have poor outcomes and limited treatment options," said Brian Schwartz, M.D., Chief Medical Officer and Head of R&D at ArQule. "ARQ 531 was rationally-designed and selected to address this unmet need by inhibiting both wild type and mutant BTK. The published crystal structure and biochemistry clearly demonstrate the mechanism by which ARQ 531 maintains binding and inhibition of mutant BTK in conditions where ibrutinib cannot."

Established Activity in Multiple Cellular and Murine Models of Hematological Malignancies

Exhibited dose dependent toxicity in human primary CLL cells (mutant and wild type)
Inhibited CLL cell migration in vitro
Established superiority to ibrutinib in an engraftment murine model of CLL
Showed activity against other B-cell signaling pathways
Demonstrated efficacy in a murine model of Richter’s transformation
John Byrd, M.D., the Warren Brown Chair of Leukemia Research at The Ohio State University stated, "The inhibition profile of ARQ 531 may confer distinct advantages over ibrutinib, potentially expanding the patient population beyond those with a C481S mutation who may benefit from treatment. Targeting multiple kinases in the B cell activation pathway may provide more durable responses to treatment while also delaying the emergence of treatment resistance. Jennifer Woyach, M.D., Associate Professor of Medicine at The Ohio State University, added, "I am particularly encouraged by the CLL mouse model data which established the superior efficacy of ARQ 531 compared to ibrutinib and the efficacy of ARQ 531 in the model of Richter’s transformation as this is an extremely aggressive disease with very few treatment options."

On August 13, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on the development of cellular immunotherapies based on its novel, universal Antibody-Coupled T Cell Receptor (ACTR) technology platform, reported that an investigational new drug (IND) application is now active for ACTR T cells in combination with trastuzumab for the treatment of patients with HER2+ advanced cancers (Press release, Unum Therapeutics, AUG 13, 2018, View Source [SID1234528936]). This represents the first solid tumor product candidate based on Unum’s novel, universal ACTR technology, and the fourth clinical trial program for the Company.

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"We are very happy to reach this important milestone for patients and for Unum," said Chuck Wilson, Chief Executive Officer of Unum. "ACTR represents a promising novel technology that can be used to target different tumor types and it’s exciting to expand its application to target solid tumors. We are committed to developing ACTR for patients with HER2+ advanced cancers who need better treatment options."

Under this IND, Unum is preparing to initiate a multi-center Phase I trial, called ATTCK-34-01, by the end of 2018 in patients with HER2+ advanced cancers. ATTCK-34-01 is designed as a dose escalation study where both the ACTR T cell drug product and trastuzumab doses are escalated in order to define the safety, tolerability, and anti-tumor activity of the combination. Expansion at the recommended Phase 2 dose is planned.

On August 13, 2018 Checkpoint Therapeutics, Inc. ("Checkpoint") (NASDAQ: CKPT), a clinical-stage immuno-oncology biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for patients with solid tumor cancers, reported that preliminary safety and efficacy data from a Phase 1/2 clinical trial of CK101 (also known as RX518), a third-generation epidermal growth factor receptor ("EGFR")
tyrosine kinase inhibitor ("TKI") being evaluated in advanced non-small cell lung cancer, has been selected for a late-breaking oral presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer, to be held September 23-26, 2018, in Toronto (Press release, Checkpoint Therapeutics, AUG 13, 2018, View Source [SID1234528977]).

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"We are thrilled to announce that preliminary data from the Phase 1/2 trial of our novel thirdgeneration EGFR inhibitor has been selected for a late-breaking oral presentation at the World Conference on Lung Cancer. This marks the first clinical data to be reported by Checkpoint, an important clinical and corporate milestone," said James F. Oliviero, President and Chief Executive Officer of Checkpoint Therapeutics. "Third-generation EGFR inhibitors are highly selective and have the potential to demonstrate improved safety and tolerability versus earlier-generation
therapies. There is currently only one third-generation EGFR inhibitor approved and we believe CK-101 could be second to market potentially with a differentiated safety profile."
Details of the presentation are as follows:

Title: CK-101 (RX518), a Third Generation Mutant-Selective Inhibitor of EGFR in NSCLC: Results of an Ongoing Phase I/II Trial
Date: Monday, Sept. 24, 2018
Session: Novel Therapies in ROS1, HER2 and EGFR
Presenter: Melissa L. Johnson, M.D., Associate Director, Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, PLLC, Nashville, Tenn.
The full abstract will be posted on the conference website on Wednesday, Sept. 5, 2018, at 5 p.m. ET. For additional information, please visit: View Source Checkpoint holds an exclusive worldwide license (except with respect to certain Asian countries) to CK‐101, which it acquired from NeuPharma, Inc. in 2015.

About CK-101
CK-101 (also known as RX518) is an oral, third-generation, irreversible kinase inhibitor against selective mutations in the EGFR gene. Activating mutations in the tyrosine kinase domain of EGFR, such as L858R and exon 19 deletion, are found in approximately 20 percent of patients with advanced non-small cell lung cancer ("NSCLC").
Compared to chemotherapy, first-generation EGFR inhibitors significantly improved objective response rate and progression-free survival in previously untreated NSCLC patients carrying EGFR mutations. However, tumor progression could develop due to resistance mutations, often within months of treatment with first-generation EGFR inhibitors. The EGFR T790M "gatekeeper" mutation is the most common resistance mutation found in patients treated with first-generation EGFR inhibitors. The mutation decreases the affinity of first-generation inhibitors to EGFR kinase domain, rendering the drugs ineffective. Second-generation EGFR inhibitors have improved
potency against the T790M mutation, but have not provided meaningful benefits in NSCLC patients due to toxicity from also inhibiting wild-type EGFR. Third-generation EGFR inhibitors are designed to be highly selective against both EGFR-TKI-sensitizing and resistance mutations, with minimal activity on wild-type EGFR, thereby improving tolerability and safety profiles. Checkpoint Therapeutics is developing CK-101 for the treatment of NSCLC patients carrying the
susceptible EGFR mutations. These include the EGFR T790M mutation in second-line NSCLC patients, as well as the EGFR L858R and exon 19 deletion mutations in first-line NSCLC patients.

On August 13, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on the development of cellular immunotherapies based on its novel, universal Antibody-Coupled T cell Receptor (ACTR) technology platform, reported financial results and provided a corporate update for the second quarter ended June 30, 2018 and recent activities (Press release, Unum Therapeutics, AUG 13, 2018, View Source [SID1234528937]).

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"In our first full quarter as a public company, we made significant progress in developing our proprietary, universal ACTR technology platform and advancing our pipeline of cellular immunotherapies through clinical development," said Chuck Wilson, CEO of Unum. "We continue to evaluate ACTR T cell potential in combination with different tumor-targeting antibodies in three ongoing multicenter Phase I trials. We expect to report preliminary data from these trials late this year. In addition, we are particularly pleased to announce that our investigational new drug (IND) application for ACTR T cells in combination with trastuzumab for the treatment of patients with HER2+ advanced cancers is now active and we are preparing to initiate a multi-center Phase I trial, ATTCK-34-01, by the end of 2018. This represents our first solid tumor product candidate based on our universal ACTR technology."

Recent Highlights

Cohort Expansion Phase of ATTCK-20-2 Phase I trial is Underway: During the quarter, Unum initiated the cohort expansion phase of the ATTCK-20-2 trial evaluating safety and anti-lymphoma activity of ACTR087 at the preliminary recommended phase 2 dose level used in combination with rituximab in patients with CD20+ relapsed or refractory (r/r) NHL. Unum expects to have updated data, including preliminary data from the cohort expansion part of the ATTCK-20-2 trial, by the end of 2018 and to report these at that time or in early 2019.

In addition, Unum has now filed a protocol amendment to the ATTCK-20-2 trial to explore ACTR087 in combination with an alternative rituximab dosing regimen from what has been studied to date. Preclinical studies have shown that the level of ACTR T cell activity depends upon the amount of the co-administered antibody. As such, ACTR087 safety and anti-tumor activity in combination with rituximab in CD20+ r/r NHL may be even further optimized by an alternative rituximab regimen. Testing of the alternative regimen will be incorporated into the expansion cohort of the study, which is already underway.
Continued Patient Enrollment and Dosing in ATTCK-20-03 Phase I trial: Unum continued to enroll and dose patients in ATTCK-20-03, a Phase I, multi-center, open-label clinical trial evaluating the safety, tolerability, and anti-lymphoma activity of ACTR707 used in combination with rituximab in patients with CD20+ r/r NHL. The Company expects to report preliminary data from the trial in the fourth quarter of 2018.

Continued Patient Enrollment and Dosing in ATTCK-17-01 Phase I trial: Unum continued to enroll and dose patients in ATTCK-17-01, a Phase I, multi-center, open-label clinical trial designed to test the safety, tolerability, and anti-myeloma activity of ACTR087 used in combination with SEA-BCMA in patients with r/r multiple myeloma. This is the first clinical trial under our collaboration with Seattle Genetics. Unum expects to report preliminary data from this study in the fourth quarter of 2018.

Active IND for First Solid Tumor ACTR Product Candidate:Unum announced that the IND for ACTR T cells used in combination with trastuzumab for the treatment of patients with HER2+ advanced cancers is now active and the Company expects to initiate clinical development for this product candidate by end of 2018.

Presented Pre-Clinical Data on ACTR Platform at American Society of Hematology (ASH) (Free ASH Whitepaper) Summit (ASH) (Free ASH Whitepaper) On Emerging Immunotherapies for Hematological Diseases: In July, Unum presented pre-clinical data on its proprietary ACTR T cells used in combination with daratumumab, a CD38-specific antibody. The Company is particularly interested in the potential benefit that CD38-targeted ACTR T cells can provide for patients with hematological malignancies, including acute myeloid leukemia and multiple myeloma. These data support Unum’s development of ACTR T cells in patients with these diseases, and against a highly-validated tumor target for which other T cell therapies have seen significant challenges.
Second Quarter 2018 Financial Results

Collaboration Revenue: Collaboration revenue recognized during the second quarter ended June 30, 2018 and 2017, of $1.7 million and $2.1 million, respectively, reflects the recognition of a portion of the $25.0 million upfront payment received from Seattle Genetics under Unum’s collaboration agreement as well as reimbursements of research and development costs by Seattle Genetics. Effective January 1, 2018, Unum adopted the new revenue recognition standard, ASC 606, which changed the manner in which the Company recognizes revenue from this collaboration agreement compared to the prior year period.

R&D Expenses: Research and development expenses were $9.1 million for the second quarter ended June 30, 2018, compared to $7.1 million for the same period last year. The increase reflects higher clinical trial costs for the active Phase I clinical trials, as well as increased personnel-related costs, materials and facility-related costs related to scaling manufacturing processes, and increased consultant costs. This was partially offset primarily by a decrease in consulting and manufacturing costs incurred for the Phase I clinical trial of ACTR087 in combination with rituximab as there was no production activity in the second quarter of 2018.

G&A Expenses: General and administrative expenses for the second quarter ended June 30, 2018, were $2.0 million, compared to $1.0 million for the same period last year. The increase is primarily due to expenses around operating as a public company and higher personnel related costs.

Net Loss: Net loss attributable to common stockholders was $9.0 million, or $0.31 per share, for the second quarter ended June 30, 2018, and $5.9 million, or $0.58 per share, for the same period last year.

Cash, Cash Equivalents and Marketable Securities: As of June 30, 2018, Unum had cash, cash equivalents, and marketable securities of $94.4 million, which includes approximately $63.9 million in net proceeds from the IPO and $5.0 million from the concurrent private placement. The Company believes that its existing cash, cash equivalents, and marketable securities, will fund operating expenses and capital expenditure requirements through at least December 2019, without considering $15.0 million in available borrowings under its loan and security agreement.