On May 17, 2021 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small molecule, MasterKey therapies, reported that it will host a webcast presentation on Wednesday, May 19, 2021 at 6:00 PM ET to discuss pharmacokinetic, safety, and preliminary efficacy data from the Phase 1 dose-escalation portion of the MasterKey-01 trial of BDTX-189 in patients with advanced solid tumors, which will also be presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 4-8, 2021 (Press release, Black Diamond Therapeutics, MAY 17, 2021, View Source [SID1234584641]).

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Conference Call and Webcast Event

A live webcast presentation will be available on the News & Events section of the Black Diamond website at www.blackdiamondtherapeutics.com. To access the presentation, please dial 833-730-3983 (United States) or 720-405-2158 (international) and reference the conference ID 1979666. A replay of the webcast will be available on the Black Diamond website following the presentation.

Abstract Details:

Title: Safety and Preliminary Efficacy from the Phase 1 Portion of MasterKey-01: A First-in-Human Dose-Escalation Study to Determine the Recommended Phase 2 Dose (RP2D), Pharmacokinetics (PK), and Preliminary Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB mutations, in Patients with Advanced Solid Malignancies
Session Type: Poster Session
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Friday, June 4, 2021 at 9:00 AM ET
Abstract ID: 3086

Title: Clinical pharmacokinetics of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study
Session Type: Poster Session
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Friday, June 4, 2021 at 9:00 AM ET
Abstract ID: 3097

Full abstracts will be published online at 5:00 PM ET on May 19, 2021 on the ASCO (Free ASCO Whitepaper) website at www.asco.org.

About BDTX-189
BDTX-189 is an orally available, irreversible, and ATP competitive small molecule inhibitor that is designed to block the function of a family of oncogenic epidermal growth factor receptor (EGFR) and ErbB-2 (epidermal growth factor receptor 2 [HER2]) proteins across a range of tumor types. BDTX-189 is designed as a MasterKey inhibitor targeting a family of previously undrugged and functionally similar oncogenic mutations in a tumor-agnostic manner. These mutations include extracellular domain allosteric mutations of HER2, as well as EGFR and HER2 kinase domain Exon 20 insertions, and additional activating oncogenic drivers of ErbB. The ErbB receptors are a group of receptor tyrosine kinases involved in key cellular functions, including cell growth and survival. BDTX-189 is also designed to spare normal, or wild-type, EGFR, which we believe has the potential to improve upon the toxicity profiles of current ErbB kinase inhibitors. Currently, there are no medicines approved by the U.S. Food and Drug Administration (FDA) to target all of these oncogenic mutations with a single therapy.

BDTX-189 is currently being evaluated in a Phase 1/2 clinical trial (MasterKey-01) in adult patients with advanced solid tumors expressing a range of alterations of ErbB receptors, including oncogenic MasterKey mutations, HER2-WT amplification, HER3 mutation, EGFR exon 19 deletion, and L858R mutation who have no standard therapy available or for whom standard therapy is considered unsuitable or intolerable. In July 2020, the FDA granted Fast Track designation to BDTX-189 for the treatment of adult patients with solid tumors harboring an allosteric HER2 mutation or an EGFR or HER2 Exon 20 insertion mutation who have progressed following prior treatment and who have no satisfactory treatment options.

On May 17, 2021 Nuvo Pharmaceuticals Inc. (TSX: MRV) (OTCQX: MRVFF) d/b/a Miravo Healthcare (Miravo or the Company), a Canadian-focused healthcare company with global reach and a diversified portfolio of commercial products, reported its financial and operational results for the three months ended March 31, 2021 (Press release, Nuvo Pharmaceuticals, MAY 17, 2021, View Source [SID1234580427]). For further details on the results, please refer to Miravo’s Management, Discussion and Analysis (MD&A) and Condensed Consolidated Interim Financial Statements for the three months ended March 31, 2021, which are available on the Company’s website (www.miravohealthcare.com). All figures are in Canadian dollars, unless otherwise noted.

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Key Developments
Three months ended March 31, 2021 include the following:

Adjusted total revenue(1) was $14.5 million, a decrease of 23% compared to $18.9 million for the three months ended March 31, 2020.
Adjusted EBITDA(1) was $4.4 million, a decrease of 45% compared to $8.0 million for the three months ended March 31, 2020.
Revenue related to Blexten and Cambia was $5.6 million, a decrease of 7% compared to revenue of $6.0 million for the three months ended March 31, 2020. Total Canadian prescriptions of Blexten and Cambia increased by 22% and 9% compared to the three months ended March 31, 2020.
The Company repaid $3.6 million (US$2.9 million) of the Amortization Loan to Deerfield Management Company, L.P. (Deerfield).
As at March 31, 2021, cash and cash equivalents were $23.8 million.
(1) Non-International Financial Reporting Standards (IFRS) financial measure defined by the Company below.

Business Update

As a result of the COVID-19 pandemic, the Company has made changes to operations to promote a healthy and safe environment for its employees, while the business continues to supply global partners, wholesalers, pharmacies, and ultimately patients, with its healthcare products. The possibility of future supply disruptions resulted in forward buying linked to the COVID-19 pandemic, which increased revenue in the three months ended March 31, 2020. It is anticipated that the COVID-19 pandemic may continue to impact the timing of revenue in future quarters and the Company will monitor market dynamics accordingly.
In April 2021, the Company filed and obtained a receipt for a final base shelf prospectus with the securities regulatory authorities in each of the provinces of Canada (the Prospectus). The Company has filed the Prospectus to maintain financial flexibility and to have the ability to offer the securities on an accelerated basis pursuant to the filing of prospectus supplements. The Prospectus is valid for a 25-month period, during which time the Company may offer and issue, from time-to-time, common shares, preferred shares, debt securities, warrants and subscription receipts, or any combination thereof, having an aggregate offering value of up to $40 million.
In February 2021, Nuvo Pharmaceuticals (Ireland) DAC trading as Miravo Healthcare (Miravo Ireland) entered into an exclusive license and supply agreement (the License Agreement) with The Mentholatum Company for the right to commercialize the Resultz formula and technology in the United States under the Mentholatum brand. Miravo Ireland will earn revenue from The Mentholatum Company pursuant to the License Agreement. It is anticipated that The Mentholatum Company will launch Resultz during the summer of 2021. Resultz is currently manufactured by the Company’s contract manufacturing partner in Europe.
In January 2021, the Company launched NeoVisc ONE 4 mL and NeoVisc + 2 mL in Canada. Both NeoVisc+ and NeoVisc ONE were issued a Medical Device License by Health Canada in September 2020 for the treatment of pain and improvement of joint functionality in patients affected by degenerative (age-related changes) or mechanical arthropathy (related to overuse) of the knee.
In January 2021, the Company’s exclusive partner for Pennsaid 2% in Switzerland, Gebro Pharma AG (Gebro Pharma), launched the product into the Swiss market, generating net sales and related royalty revenue for Miravo.
"Our key promoted brands, Blexten and Cambia, continued their solid performance and demonstrated year-over-year gains in prescription growth. New prescriptions of Blexten (a measure of new patients to the product) grew by 17% compared to Q1 2020. Wholesaler and pharmacy buying patterns reverted to more traditional levels, as we did not see a repeat of the forward buying that occurred in Q1 2020 in response to the uncertainty around the COVID-19 pandemic. Our recently launched Suvexx and NeoVisc brands are performing according to plan and are already achieving meaningful market share. Feedback from healthcare providers and patients in relation to both products has been encouraging. In a recent market research study conducted for our marketing team, 95% of physicians surveyed, expect to increase the number of Suvexx prescriptions for their migraine patients," said Jesse Ledger, Miravo’s President & CEO. "We remain optimistic that with the accelerated roll out of COVID-19 vaccination programs across Canada and around the world, patients will gain improved access to healthcare providers during the remainder of the year and we anticipate this will result in demand for products across all our business segments."

First Quarter 2021 Financial Results
Adjusted total revenue was $14.5 million for the three months ended March 31, 2021 compared to $18.9 million for the three months ended March 31, 2020. For the three months ended March 31, 2021, the decrease in the Licensing and Royalty Business segment was primarily due to a $2.2 million decrease of the royalty earned on U.S. net sales of Vimovo due to a competitor launching a generic version of Vimovo in March 2020. During the three months ended March 31, 2021, the Company received a royalty of 10% based on U.S. net sales of Vimovo. In subsequent quarters, this royalty is anticipated to decrease to 5% of U.S. net sales of Vimovo due to a royalty step-down provision in Miravo Ireland’s license agreement with Horizon Therapeutics plc that is anticipated to be triggered as a result of continued generic competitor market share gains. Adjusted total revenue attributable to the Commercial Business segment declined during the three months ended March 31, 2021, as an increase in sales related to certain promoted products was more than offset by a decline in revenue from the segment’s mature products. During the comparative quarter, the possibility of future supply disruptions resulted in forward buying linked to the COVID-19 pandemic, which increased revenue in the Company’s Commercial Business segment in the three months ended March 31, 2020. The Production and Service Business segment revenue decreased as a result of a decline in the Company’s Resultz product sales.

Adjusted EBITDA was $4.4 million for the three months ended March 31, 2021 compared to $8.0 million for the three months ended March 31, 2020. The decrease in the current quarter was primarily attributable to a decrease in gross profit and an increase in sales and marketing expenses, slightly offset by a decrease in general and administrative expenses.

Non-IFRS Financial Measures
The Company discloses non-IFRS measures (such as adjusted total revenue, adjusted EBITDA, adjusted EBITDA per share and cash value of loans) that do not have standardized meanings prescribed by IFRS. The Company believes that shareholders, investment analysts and other readers find such measures helpful in understanding the Company’s financial performance and in interpreting the effect of the Aralez Transaction and the Deerfield Financing on the Company. Non-IFRS financial measures do not have any standardized meaning prescribed by IFRS and may not have been calculated in the same way as similarly named financial measures presented by other companies.

Adjusted Total Revenue
The Company defines adjusted total revenue as total revenue, plus amounts billed to customers for existing contract assets, less revenue recognized upon recognition of a contract asset. Management believes adjusted total revenue is a useful supplemental measure to determine the Company’s ability to generate cash from its customer contracts used to fund its operations.

The following is a summary of how adjusted total revenue is calculated:

Adjusted EBITDA
EBITDA refers to net income (loss) determined in accordance with IFRS, before depreciation and amortization, net interest expense (income) and income tax expense (recovery). The Company defines adjusted EBITDA as EBITDA, plus amounts billed to customers for existing contract assets, inventory step-up expenses, stock-based compensation expense, Other Expenses (Income), less revenue recognized upon recognition of a contract asset and other income. Management believes adjusted EBITDA is a useful supplemental measure to determine the Company’s ability to generate cash available for working capital, capital expenditures, debt repayments, interest expense and income taxes.

The following is a summary of how EBITDA and adjusted EBITDA are calculated:

1) The Company’s derivative liabilities are measured at fair value through profit or loss at each reporting date. As a result of the increase in the share price in the current quarter and an increase in the volatility of the Company’s shares, amongst other inputs, the value of the Company’s derivative liabilities increased and the Company recognized a net non-cash $18.4 million loss on the change in fair value of derivative liabilities for the three months ended March 31, 2021.

Virtual Annual Meeting of Shareholders
Miravo’s 2021 Annual Meeting of Shareholders (Meeting) will be held as an online meeting only. The Meeting will take place on Monday, May 17, 2021 (today) at 9:00 a.m. Registered shareholders can attend the Meeting online, vote shares electronically if they have not voted by proxy in advance of the Meeting in accordance with the proxy instructions, and submit questions during the Meeting. You will need to have your 16-digit Control Number (the Control Number) to participate in the Meeting. If you are a shareholder and do not have a Control Number or if you are not a Miravo shareholder, you can attend the Meeting as a guest, but you will not be able to vote at the Meeting.

The link to participate in the Meeting is: www.virtualshareholdermeeting.com/mrv2021. If you encounter any difficulties accessing the virtual meeting during the check-in or meeting time, please call the technical support number that will be posted on the Virtual Shareholder Meeting log in page.

On May 17, 2021 Wugen reported that it is adding a new subset of NK cells to the cell therapy toolkit with its memory NK cell approach, which may lead to high antitumor efficacy without requiring a CAR or other modifications (Press release, Wugen, MAY 17, 2021, View Source [SID1234580426]).

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The company was formed in 2018 to develop off-the-shelf CAR T cell therapies, but broadened its scope to include memory NK cells after in-licensing the technology from Washington University in St. Louis last year.

Now, it has programs for both cell types running in parallel, with each expected to start clinical development next half.

Unmodified NK cells have historically fallen short on efficacy, and companies have increasingly turned to the addition of a tumor antigen-specific CAR to harness and concentrate activity against the tumor. CAR NK cells are attracting broad industry attention as clinical validation builds.

"NK cell platforms are now really coming to the fore in industry in terms of the realization that off-the-shelf, allogeneic NK cells will be competitive against CAR T cells," said Daniel Kemp, who joined Wugen as CEO this month after serving as VP and head of cell therapies BD & operations at Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK).

Wugen thinks its memory NK cells may attain high levels of efficacy without a CAR.

CMO Jan Davidson told BioCentury memory NK cells are a subset with an enhanced effector function. Specifically, they express more activating receptors and have fewer inhibitory signals. They also produce more cytotoxic effector molecules and cytokines to activate downstream components of the immune system, and they persist longer.

He added that most NK cell therapies aren’t enriched for the memory NK subpopulation because the subtype is formed through a process that naturally occurs in the tumor, but NK cell therapies are usually sourced from cord blood or induced pluripotent stem cells.

The company has an in vitro process for converting NK cells harvested from healthy donors into the memory phenotype using cytokines to drive them into a highly activated functional state.

The memory NK cells have been tested in investigator-initiated studies at Washington University in St. Louis in several acute myelogenous leukemia (AML) settings. Next, Wugen plans to begin a study in the relapsed/refractory population.

"We’re building on the existing data in AML, where there’s a high unmet need and the cells can be potentially curative. This is a quick path to develop this strategy and be able to help patients in short order, but after that, there are a lot of different opportunities," said Ryan Sullivan, VP and head of NK research at Wugen.

Davidson noted that the company has strong preclinical evidence of efficacy in solid tumors.

Kemp added that the company will explore engineered versions of the cells as well, "whether through CAR mechanisms or other types of modifications."

In solid tumors, Sullivan told BioCentury there’s an opportunity to combine the NK cells with mAbs that act via antibody-dependent cellular toxicity (ADCC) — a process that recruits NK cells to kill the antibody-bound tumor cells. Many cancer therapies including anti-CTLA-4 mAb Yervoy ipilimumab heavily rely on ADCC for therapeutic efficacy, and are less effective in patients with compromised innate immune systems.

"A lot of the patients who these mAbs are administered to have some level of immunosuppression, so there’s a poor response, but we’re providing the engine to potentiate the ADCC capability," said Sullivan.

Kemp noted Wugen is interested in building strategic relationships around the ADCC mechanism.

With its allogeneic CAR T cell platform, Wugen is first tackling T cell malignancies. The indication has proven challenging because when designed to hit a T cell target on malignant cells, the CAR Ts can destroy themselves through fratricide. Wugen is sidestepping fratricide by deleting CD7.

At least four companies have CAR T cell therapies in development to treat T cell cancers. Davidson and Sullivan aren’t aware of other companies developing memory NK cell therapy products.

In March, Wugen granted development, manufacturing and commercialization rights to Alpha Biopharma Inc. for its universal memory NK and CAR T cells for certain cancers in mainland China, Hong Kong, Macao, Taiwan and Singapore. The same month, it signed a deal with HCW Biologics Inc. to use its fusion molecules in the manufacturing of Wugen’s cell therapies.

The company raised $36 million in a series A round, and is currently raising a series B round.

On May 17, 2021 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to treat ESR1-mutated metastatic breast and gynecological cancers, reported the publication of its scholarly article, "Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer," in the peer-reviewed journal Breast Cancer Research (Press release, Sermonix Pharmaceuticals, MAY 17, 2021, View Source [SID1234580244]). The paper details positive findings from a preclinical study of lasofoxifene, a selective estrogen receptor modulator (SERM), in mouse models of endocrine therapy-resistant breast cancer.

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In this study, luciferase-GFP tagged MCF7 cells bearing wild-type, Y537S or D538G estrogen receptor alpha (ERα) mutations were injected into the mammary ducts of NSG mice, which were subsequently treated with lasofoxifene or fulvestrant as single agents or in combination with palbociclib, a CDK4/6 inhibitor that blocks cell-cycle progression. Tumor growth and metastasis were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements and histological analysis.

As a monotherapy, lasofoxifene was found to be more effective in this preclinical model than fulvestrant at inhibiting primary tumor growth and reducing metastases. Adding palbociclib improved the effectiveness of both lasofoxifene and fulvestrant for tumor suppression and metastasis prevention at four distal sites (lung, liver, bone and brain), with the combination of lasofoxifene/palbociclib showing more potency than that of fulvestrant/palbociclib.

"The results of this study demonstrate, for the first time, the anti-tumor activity of lasofoxifene in mouse models of endocrine therapy-resistant breast cancer harboring ESR1 mutations, and its superiority to fulvestrant in this preclinical model," said Barry Komm, Ph.D., Sermonix chief scientific officer and co-author of the manuscript. "These findings support continued development of this promising compound in a clinical setting. I look forward to data from our ongoing ELAINE 1 Phase 2 clinical study, which is evaluating lasofoxifene versus fulvestrant, early next year."

Endocrine therapy resistance, driven in part by more widespread use of aromatase inhibitors, represents a significant challenge in the treatment of ER+ metastatic breast cancer and highlights the urgent need for more effective interventions, according to Dr. Geoffrey Greene, the study’s lead investigator.

"The results of this study convincingly demonstrate that lasofoxifene suppresses tumor growth and metastases in human-derived xenograft models harboring the Y537S and D538G ESR1 mutations, the most commonly observed ERα mutations," said Dr. Greene, M.D., Ph.D., chair of the Ben May Department for Cancer Research at the University of Chicago. "I believe this compound, with notable activity on breast cancer models with ESR1 mutations, combined with a long half-life and high bioavailability, has the potential to present a differentiated profile to current hormonal treatments in overcoming the acquired resistance that limits their long-term effectiveness. I am eager to see results from in-human studies."

The paper can be accessed online at: View Source

On May 17, 2021 Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines, reported an exclusive license and collaboration agreement with Ji Xing Pharmaceuticals (Ji Xing) to develop and, if approved, commercialize the investigational drug etripamil in patients with paroxysmal supraventricular tachycardia (PSVT) and additional cardiovascular conditions in Greater China (Press release, Milestone Pharmaceuticals, MAY 17, 2021, View Source [SID1234580243]). Ji Xing is a biotechnology company headquartered in Shanghai and backed by RTW Investments, LP (RTW) focused on advancing innovative medicines in China.

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"This agreement marks an important step toward realizing our vision for etripamil to benefit patients living with PSVT globally while strengthening our balance sheet and executional capabilities through partnership," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. "We look forward to partnering with the talented team at Ji Xing to develop and commercialize this promising therapy in the licensed regions."

"Etripamil has the potential to change the treatment paradigm for PSVT and could serve as a meaningful new therapeutic option for patients," said Peter Fong, Chief Executive Officer of Ji Xing and Head of Company Creation at RTW. "We are delighted to expand Ji Xing’s cardiovascular focus by partnering with Milestone and look forward to unlocking the full therapeutic potential of etripamil for patients with PSVT in China."

Under the terms of the agreement, Milestone will grant Ji Xing an exclusive license to develop and, if regulatory approval is obtained, commercialize etripamil in patients with PSVT in Greater China. Milestone will receive an upfront cash payment consisting of $15 million and a $5 million equity investment by RTW. In addition, Milestone is eligible to receive up to $107.5 million in milestone payments and royalties on future sales of etripamil in Greater China. Milestone will supply etripamil and delivery devices to Ji Xing. Ji Xing will be responsible for development and commercialization costs in Greater China.

About Paroxysmal Supraventricular Tachycardia

Paroxysmal supraventricular tachycardia (PSVT) is a rapid heart rate condition characterized by intermittent episodes of supraventricular tachycardia (SVT) that start and stop suddenly and without warning that affects approximately two million Americans. Episodes of SVT are often associated with symptoms including palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting, and anxiety. Certain calcium channel blockers have long been approved for the treatment of PSVT as well as other cardiac conditions. However, calcium channel blockers approved for the termination of SVT episodes must be administered intravenously under medical supervision, usually in an emergency department or other acute care setting.

About Etripamil

Etripamil, Milestone’s lead investigational product, is a novel calcium channel blocker designed to be a rapid-response therapy for episodic cardiovascular conditions. As a nasal spray that is self-administered by the patient, etripamil has the potential to shift the current treatment experience for many patients from the emergency department to the at-home setting. Milestone is conducting a comprehensive development program for etripamil, with Phase 3 trials ongoing in paroxysmal supraventricular tachycardia (PSVT) and a Phase 2 proof-of-concept trial is now underway in patients with atrial fibrillation and rapid ventricular rate (AFib-RVR).