On March 2, 2021 MannKind Corporation (Nasdaq: MNKD) reported the pricing of $200.0 million aggregate principal amount of 2.50% Convertible Senior Notes due 2026 (the "notes") in a private placement (the "offering") to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Mannkind, MAR 2, 2021, View Source [SID1234575901]). MannKind also granted the initial purchasers of the notes an option to purchase, within a 13-day period beginning on, and including, the date on which the notes are first issued, up to an additional $30.0 million aggregate principal amount of notes. The sale of the notes is expected to close on March 4, 2021, subject to customary closing conditions.

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The notes will be general unsecured obligations of MannKind and will accrue interest at a rate of 2.50% per annum, payable semiannually in arrears on March 1 and September 1 of each year, beginning on September 1, 2021. The notes will mature on March 1, 2026, unless earlier converted, redeemed or repurchased.

Before December 1, 2025, holders will have the right to convert their notes only upon the occurrence of certain events. From and after December 1, 2025, until the close of business on the business day immediately preceding the maturity date, holders will have the right to convert all or any portion of their notes at their election. Upon conversion, MannKind will pay or deliver, as the case may be, cash, shares of MannKind’s common stock or a combination of cash and shares of MannKind’s common stock, at its election. The initial conversion rate is 191.8281 shares of common stock per $1,000 principal amount of notes, which represents an initial conversion price of approximately $5.21 per share of common stock. The initial conversion price represents a premium of approximately 30% over the last reported sale of $4.01 per share of MannKind’s common stock on March 1, 2021. The conversion rate and conversion price will be subject to adjustment upon the occurrence of certain events.

MannKind may not redeem the notes prior to March 6, 2024. MannKind may redeem for cash all or any portion of the notes (subject to certain limitations), at its option, on or after March 6, 2024 and prior to the 36th scheduled trading day immediately preceding the maturity date, if the last reported sale price of MannKind’s common stock has been at least 130% of the conversion price then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period (including the last trading day of such period) ending on, and including, the trading day immediately preceding the date on which MannKind provides notice of redemption at a redemption price equal to 100% of the principal amount of the notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

If a "fundamental change" (as defined in the indenture for the notes) occurs, then, subject to limited exceptions, holders may require MannKind to repurchase their notes for cash. The repurchase price would be equal to the principal amount of the notes to be repurchased, plus accrued and unpaid interest, if any, to, but excluding, the applicable repurchase date.

MannKind estimates that the net proceeds from the offering will be approximately $193.8 million (or approximately $222.9 million if the initial purchasers fully exercise their option to purchase additional notes), after deducting the initial purchasers’ discounts and commissions and estimated offering expenses. MannKind intends to use the net proceeds from this offering for working capital and other general corporate purposes, including a Phase 3 clinical trial of Afrezza in pediatric subjects and further development of product candidates in MannKind’s pipeline. MannKind may also use a portion of the proceeds from this offering to pay down a portion of existing debt or for acquisitions or strategic investments in complementary businesses or technologies, although MannKind does not currently have any plans for any such debt repayment, acquisitions or investments.

The notes and any shares of MannKind’s common stock issuable upon conversion of the notes have not been and will not be registered under the Securities Act, any state securities laws or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any of these securities nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification thereof under the securities laws of any such state or jurisdiction.

On March 2, 2021 Cardinal Health Specialty Solutions reported that it is making important strides in cancer research using real-world evidence (RWE) (Press release, Cardinal Health, MAR 2, 2021, View Source [SID1234575923]). Research developed by Cardinal Health, published today in the Journal of the American Medical Association, suggests that RWE may be able to be applied more broadly in cancer research and regulatory filings, and could lead to accelerated clinical trials in cancer research . Real-world evidence is generated during routine clinical practice and outside the context of randomized controlled trials.

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"The potential to use RWE to complement and supplement traditional data from randomized controlled trials is exciting because it could significantly accelerate the speed at which clinical trials are conducted, and as a result, innovative medicines could be approved and reach patients faster," said Bruce Feinberg, DO, Chief Medical Officer at Cardinal Health Specialty Solutions and lead author of the study.

Although randomized controlled trials remain the standard for assessing the safety and efficacy of new cancer therapies, there is increasing recognition that this research method is costly, time consuming and does not accurately represent the general population. These factors – combined with the growth of targeted therapies and the rapidly expanding field of drug development – have researchers and policy makers like the Federal Drug Administration (FDA) exploring how real-world evidence can be used to accelerate the drug development process.

The Cardinal Health study included 956 patients who were receiving first-line treatment for thyroid cancer, breast cancer or melanoma between 2014 and 2017. The research used a novel, real-world application of the Response Evaluation Criteria in Solid Tumors (RECIST) methodology to assess how the patients’ tumors responded to the therapy.

"The study findings show that applying RECIST methodology to real-world data may allow for accurate comparisons between real-world data and RCT data in solid tumors. We believe these findings may open the door for broader use of RWE across many areas of cancer research," said Ajeet Gajra, MD, Sr. Medical Director at Cardinal Health and one of the co-authors of the study.

On March 2, 2021 MannKind Corporation (Nasdaq: MNKD), a company focused on the development and commercialization of inhaled therapeutic products for patients with endocrine and orphan lung diseases, reported that its Chief Executive Officer, Michael Castagna, PharmD, will present at the H.C. Wainwright Global Life Sciences Conference which will be available on demand starting on March 9, 2021 at 7:00 am (ET) (Press release, Mannkind, MAR 2, 2021, View Source [SID1234575939]). Interested parties can access a link to the on demand webcast of the presentation from the Events & Presentations section of the Company’s website at View Source The webcast replay will remain available for 14 days following the live presentation.

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On March 2, 2021 Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported that the Company will participate in the virtual H.C. Wainwright Global Life Sciences Conference (Press release, Verastem, MAR 2, 2021, View Source [SID1234575955]). The fireside chat will be made available for on-demand listening beginning Tuesday, March 9, 2021 at 7:00 a.m. EST.

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The webcast of the fireside chat will be available on the "Media" section of the Company’s website at www.verastem.com under "Events & Presentations".

On March 2, 2021 Epizyme, Inc. (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company developing and delivering novel epigenetic therapies, reported outlining the Company’s strategic vision and focus on oncology treatment with the Company’s epigenetic pipeline (Press release, Epizyme, MAR 2, 2021, View Source [SID1234575971]). A link to the presentation and slideshow can be found here.

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"The recent accelerated approvals of TAZVERIK in Epithelioid Sarcoma and Relapsed / Refractory Follicular Lymphoma are, of course, the critical foundation on which we will continue to expand Epizyme’s mission of rewriting treatments for cancer through novel epigenetic medicines," said Robert Bazemore, President and Chief Executive Officer of Epizyme. "We believe TAZVERIK has the potential to become a backbone of treatment across lines of ES and FL therapy. Beyond that, we are focused on developing the pipeline-in-a-drug potential we see in TAZVERIK, while expanding our portfolio and bringing novel oncology therapeutics into clinical development. We aspire to change the standard of care for patients and physicians by developing targeted medicines with fundamentally new mechanisms of action directed at specific causes of cancers."

"I am really excited about Epizyme’s comprehensive and innovative clinical development plan both for tazemetostat and our pipeline, for which we anticipate a steady stream of data," said Dr. Shefali Agarwal, Epizyme’s, EVP, Chief Medical and Development Officer. "Our aim is to demonstrate the benefits of tazemetostat to patients in earlier lines of treatment for ES and FL by exploring various combinations with standard of care therapies. We also plan to further explore tazemetostat as both monotherapy and in combinations across multiple new hematologic and solid tumor cancers. Our experience and platform have led to an incredibly rich pipeline of both clinical and discovery programs targeting several classes of epigenetic modulators and we expect that many these programs will be entering clinical trials in the next several years."

Highlights from the Next EPIsode call included:

Preliminary Data from Confirmatory Phase 1b/3 Study EZH-302 in Follicular Lymphoma

The combination of TAZVERIK + R2 (Lenalidomide and Rituximab) is being evaluated in the Phase 1b safety run-in portion of the EZH-302 trial, which enrolled a total of 13 patients. Among the 13 patients evaluated in this standard dose escalation design, no Dose Limiting Toxicities (DLTs) were observed during the first cycle of treatment up to the highest dose of 800mg of TAZVERIK twice daily. As of mid-February, initial data from the trial also showed:

All but one of the 13 patients enrolled remain on therapy, and, to date, seven of the patients were also considered evaluable for efficacy based on the availability of tumor scans from investigators.
All seven evaluable patients demonstrated a response to treatment with TAZVERIK+R2 with three complete responses (CR) and four partial responses (PR).
The safety profile of TAZVERIK + R2 observed in these patients to date is consistent with that previously described with the respective drugs; no patients have discontinued due to an adverse event.
Based on these early safety and activity findings, Epizyme is preparing to commence the Phase 3 randomization portion of the trial. The Company plans to present further data from the Phase 1b portion of the study at a medical meeting in 2021.

Preliminary Data from Phase 1b/2 Study EZH-1101 In Prostate Cancer

The combination of tazemetostat with standard of care treatments, enzalutamide or abiraterone, is being evaluated in the Phase 1b safety run-in portion of the EZH-1101 trial, which enrolled a total of 21 men with metastatic prostate cancer. Among the 21 patients enrolled in a standard dose escalation design, no DLTs were observed at any dose of tazemetostat up to a maximum dose of 1600mg twice daily. As of mid-February, initial data from the trial also showed:

Seven out of 21 patients had a PSA response of ≥50%; one additional patient had a PSA response of ≥35%.
Six of the PSA50 responses were in the tazemetostat + enzalutamide cohort and one was in the tazemetostat + abiraterone/prednisone cohort.
The Company also observed a 47% disease control rate to-date and presented an example of radiographic response in a patient achieving a partial response (PR) in the trial.
The Company highlighted that all responses were in ARV7 negative patients using the EPIC platform, considered more rigorous in detecting ARV7 status. Only one ARV7 positive patient was enrolled in the safety run-in portion of the trial.
Based on these early safety and activity findings, Epizyme recently initiated enrollment in the Phase 2 efficacy portion of the trial. The Company plans to present further data from the Phase 1b portion of the study at a medical meeting in 2021.

Initiation of Basket Trials in Additional Heme and Solid Tumors Planned in Second Half 2021

Epizyme will initiate two signal finding basket studies to evaluate tazemetostat safety and efficacy across multiple new types of heme and solid tumors. With this approach, the Company will study multiple combinations with standard of care therapies and novel mechanisms of action to expand the potential of TAZVERIK to patients and the physicians who treat them. Epizyme announced on today’s call that it plans to initiate both basket studies in the second half of 2021.

Advancing Epizyme’s Novel SETD2 Inhibitor Program into the Clinic in 2021

SETD2 is a histone methyltransferase, similar to EZH2, which plays multiple important roles in oncogenesis. Based on the promise of SETD2 inhibition in multiple settings, including high risk t(4;14) multiple myeloma and in other B-cell malignancies such as large-cell lymphoma, as well as in combination with existing and emerging therapies including tazemetostat, Epizyme is planning to submit an IND (Investigational New Drug) application with the FDA in mid-2021.

"We are extremely excited about the potential for our SETD2 program and breadth of our growing discovery pipeline. Our ambition is to deliver at least five of these programs to the clinic in the next five years," said Jeffery Kutok, M.D., Ph.D, Epizyme’s Chief Scientific Officer. "We look forward to continuing to update you on the considerable number of promising compounds against important oncology targets in our pipeline as they move toward clinical development, furthering Epizyme’s mission of delivering medicines that can make meaningful differences in the lives of patients with cancer."

On the call today, the company reiterated its financial strength, with cash expected to be sufficient to fund these initiatives into 2023. Additionally, Epizyme plans to continue to evaluate collaborations with companies with an established commercial presence outside the United States, as well as potential clinical trial collaborations involving drugs where a tazemetostat combination makes sense. The scientific advice process with the European Medicines Evaluation Agency (EMEA) for tazemetostat in follicular lymphoma has begun and Epizyme will provide more details from these interactions and the path ahead later this year.

"As we consider the next five years, we expect to be the preferred partner of choice for accessing innovation in epigenetics. We have established a deep biological understanding of how best to evaluate novel, best in class epigenetic targets and, importantly, ensuring the right translational insights are captured early," said Matthew Ros, EVP, Chief Strategy and Business Officer. "We plan to leverage clinical and research collaborations to expand our ability to interrogate multiple investigative therapies with partners with like-minded scientific interests and expertise."

Next EPIsode Presentation and Slideshow

A replay of today’s webcast and the full slideshow presentation can be accessed and downloaded by visiting the Investor section of the Company’s website at www.epizyme.com.