Cytokinetics Announces Proposed Public Offering of Convertible Senior Notes

On November 6, 2019 Cytokinetics, Incorporated (Nasdaq: CYTK) reported that it expects to sell, subject to market and other conditions, an aggregate of $100.0 million principal amount of its convertible senior notes due 2026, or the notes, in an underwritten public offering (Press release, Cytokinetics, NOV 6, 2019, View Source [SID1234550641]). Cytokinetics expects to grant the underwriters a 30-day option to purchase up to an additional $15.0 million aggregate principal amount of the notes in connection with the offering, solely to cover over-allotments. All of the notes will be sold by Cytokinetics.

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The notes will be senior unsecured obligations of Cytokinetics and will accrue interest payable semiannually in arrears. The notes will be convertible in certain circumstances into cash, shares of Cytokinetics’ common stock, or a combination of cash and shares of Cytokinetics’ common stock, at Cytokinetics’ election. The interest rate, initial conversion rate and other terms of the notes will be determined at the time of the pricing of the offering.

Cytokinetics intends to use the net proceeds from the proposed offering to fund (i) the continued development of and commercial readiness activities associated with omecamtiv mecarbil, (ii) the continued clinical development of CK-274 and related compounds in indications associated with hypertrophic cardiomyopathies and related diseases associated with diastolic dysfunction and cardiac fibrosis, including heart failure with preserved ejection fraction, (iii) the continued clinical development of reldesemtiv in patients with amyotrophic lateral sclerosis and spinal muscular atrophy, including potential Phase 3 clinical trials and other commercial readiness activities, and (iv) working capital and other general corporate purposes, including tenant improvement of the new facility Cytokinetics plans to move into in 2021, capital expenditures, debt service or retirement of debt, including existing debt outstanding under Cytokinetics’ loan and security agreement. Cytokinetics also intends to use a portion of the net proceeds from the proposed offering to pay the cost of the capped call transaction described below.

In connection with the pricing of the notes, Cytokinetics expects to enter into a privately negotiated capped call transaction (together with any additional capped call transactions entered into in connection with the exercise by the underwriters of their over-allotment option as described below, the capped call transactions) with one of the underwriters in the offering or its affiliate, or the capped call counterparty. The capped call transactions will cover, subject to customary adjustments, the number of shares of Cytokinetics’ common stock that will initially underlie the notes. The capped call transactions are generally expected to reduce the potential dilution of Cytokinetics’ common stock and/or offset any cash payments Cytokinetics is required to make in excess of the principal amount of converted notes, as the case may be, as a result of any conversion of the notes, with such reduction and/or offset subject to a cap. If the underwriters in the offering exercise their over-allotment option, Cytokinetics expects to use a portion of the net proceeds from the sale of the additional notes to enter into an additional capped call transaction with the capped call counterparty.

In connection with establishing its initial hedge of the capped call transactions, the capped call counterparty or its affiliates expect to purchase shares of Cytokinetics’ common stock and/or enter into various derivative transactions with respect to Cytokinetics common stock concurrently with or shortly after the pricing of the notes, including with certain investors in the notes. This activity could increase (or reduce the size of any decrease in) the market price of Cytokinetics’ common stock or the notes at that time.

In addition, the capped call counterparty or its affiliates may modify its hedge positions by entering into or unwinding various derivatives with respect to Cytokinetics’ common stock and/or purchasing or selling Cytokinetics’ common stock or other securities of Cytokinetics in secondary market transactions following the pricing of the notes and prior to the maturity of the notes (and are likely to do so on each exercise date of the capped call transaction, which are expected to occur during the 60 trading day period beginning on the 61st scheduled trading day prior to the maturity date of the notes, or following any termination of any portion of the capped call transaction in connection with any repurchase, redemption or early conversion of the notes). This activity could also cause or avoid an increase or decrease in the market price of Cytokinetics’ common stock or the notes, which could affect noteholders’ ability to convert the notes and, to the extent the activity occurs during any observation period related to a conversion of the notes, affect the amount and value of the consideration that noteholders will receive upon conversion of the notes.

Morgan Stanley & Co. LLC and Mizuho Securities are acting as joint book-runners for the offering. JMP Securities is acting as lead manager.

An automatic shelf registration statement relating to the notes was previously filed with the Securities and Exchange Commission, or SEC, and became immediately effective on November 6, 2019. The offering will be conducted by means of prospectus supplement and accompanying prospectus. The preliminary prospectus supplement and the accompanying prospectus relating to and describing the terms of the proposed offering is expected to be filed with the SEC and, if and when filed, will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus related to the offering may also be obtained by contacting: Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014; or Mizuho Securities USA LLC, Attn: Equity Capital Markets, 320 Park Avenue, 12th Floor, New York, NY 10022-6815, by telephone (212) 205-7600, or by email: [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the notes, nor shall there be any sale of the notes in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Sangamo Therapeutics Reports Third Quarter 2019 Financial Results

On November 6, 2019 Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, reported third quarter 2019 financial results and recent business highlights (Press release, Sangamo Therapeutics, NOV 6, 2019, View Source [SID1234550640]).

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"We continue to prioritize and progress our clinical development programs, as demonstrated by the accepted ASH (Free ASH Whitepaper) poster presentations for our two most advanced programs, SB-525 hemophilia A gene therapy and ST-400 beta thalassemia cell therapy. Patients are currently being screened for enrollment into the clinical study evaluating ST-920, our wholly owned Fabry disease gene therapy, and we expect to enroll a first patient by the end of the year. We have also recently submitted a CTA for the clinical trial of our CAR-Treg, TX200, in mismatched renal transplantation," said Sandy Macrae, CEO of Sangamo. "As it is important that we continue to articulate our drug development, research, and partnership strategies, we will host a Sangamo R&D day in New York on December 17, 2019. At this meeting, we will provide updates across our various genomic medicine programs, offer our perspective on the clinical data at ASH (Free ASH Whitepaper), share improvements across our technology platforms, and provide an overview of the manufacturing strategy to support our clinical and commercial supply."

Recent Highlights

Clinical

Earlier today, announced the upcoming poster presentation of three abstracts at the 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in Florida:
Updated follow-up of the Phase 1/2 Alta Study assessing SB-525 gene therapy in adult patients with severe hemophilia A in partnership with Pfizer.
Preliminary information from the Phase 1/2 THALES Study assessing ST-400 ex vivo gene-edited cell therapy in patients with transfusion-dependent beta thalassemia in partnership with Sanofi.
In vitro results of zinc finger nuclease-mediated disruption of BCL11A erythroid enhancer in erythroid cells derived from patients with sickle cell disease.
Significant progress made on advancing the transfer of SB-525 development to our partner Pfizer, who will run the Phase 3 registrational clinical trial, including completing manufacturing technology transfer and initiating transfer of the investigational new drug application (IND). Pfizer announced it has enrolled its first patient in the 6-month lead-in study, which is expected to serve as a baseline control for the patients who are enrolled into the Phase 3 study.
Activated a fourth US clinical site for the STAAR study evaluating ST-920, an investigational gene therapy candidate for Fabry disease. Sangamo is currently screening patients in the US for enrollment into the clinical study and expects to enroll the first patient this year.
Received approval of the clinical trial authorization application (CTA) for ST-920, allowing expansion of the study into the UK. Additionally, the FDA granted Orphan Drug Designation to ST-920 for the treatment of Fabry disease.
Following the dosing of a third patient in the THALES Study, Sangamo achieved a $6.0M milestone with Sanofi and received $2.1M from the California Institute for Regenerative Medicine (CIRM). Enrollment of all 6 patients in the Phase 1/2 study is expected to be completed in 2019.
Sanofi is currently recruiting patients into the Phase 1/2 PRECIZN-1 trial evaluating BIVV003 gene-edited cell therapy for the treatment of sickle cell disease.
Filed the CTA for TX200, a CAR-Treg product candidate, in HLA-A2 mismatched kidney transplantation.
Kite, a Gilead Company, is planning to initiate a clinical study of KITE-037, an allogeneic anti-CD19 CAR-T cell product, in 2020.
Corporate

Announced Sangamo R&D day to be held in New York City on December 17, 2019.
Hired Sung Lee as Executive Vice President and Chief Financial Officer.
Hired Bettina Cockroft as Senior Vice President and Chief Medical Officer.
Promoted R. Andrew Ramelmeier to Executive Vice President, Technical Operations.
Third Quarter 2019 Financial Results

For the third quarter ended September 30, 2019, Sangamo reported a consolidated net loss of $27.3 million, or $0.24 per share, compared to a net loss of $12.8 million, or $0.13 per share, for the same period in 2018. As of September 30, 2019, the Company had cash, cash equivalents, and investments of $408.3 million.

Revenues for the third quarter ended September 30, 2019 were $22.0 million, compared to $23.6 million for the same period in 2018. The decrease of $1.6 million was primarily driven by the decrease of $7.0 million in revenues related to Pfizer and $1.4 million related to royalty revenues offset by increases of $6.5 million in revenues related to Sanofi as the Company achieved a $6.0 million milestone upon dosing the third subject in the Phase 1/2 THALES study in August 2019.

As anticipated, operating expenses increased in the third quarter, reflecting the Company’s growth through increased U.S. headcount in support of growth of the clinical development programs and preclinical pipeline, and manufacturing-readiness activities. Total operating expenses for the third quarter ended September 30, 2019 were $51.2 million, compared to $39.8 million for the same period in 2018. Research and development expenses were $36.3 million for the third quarter of 2019, compared to $28.8 million for the same period in 2018. The increase is primarily due to higher compensation costs from headcount growth, higher facility expenses related to our new Brisbane facility, and higher manufacturing expenses related to our clinical activities. General and administrative expenses were $14.9 million for the third quarter of 2019, compared to $11.0 million for the same period in 2018. The increase was primarily due to increased compensation costs due to headcount growth and increased facility expenses. Construction of our in-house manufacturing capability in Brisbane is proceeding on schedule, and we still expect to commence Good Manufacturing Practice (GMP) qualification procedures early next year.

Financial Guidance for 2019

Operating Expense: Sangamo expects operating expense of $210.0 to $220.0 million for the year ending December 31, 2019.
Cash and Investments: Sangamo projects that current cash, cash equivalents, and investments should provide funds for operations through year end 2021.
Conference Call

Sangamo will host a conference call today, November 6, 2019, at 5:00 p.m. Eastern Time, which will be open to the public. The call will also be webcast live and can be accessed via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 7276749. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 7276749.

Geron Announces Two Poster Presentations at Upcoming American Society of Hematology Annual Meeting

On November 6, 2019 Geron Corporation (Nasdaq: GERN) reported that two abstracts related to imetelstat, the Company’s first-in-class telomerase inhibitor, have been accepted for presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition to be held in Orlando, Florida from December 7-10, 2019 (Press release, Geron, NOV 6, 2019, View Source [SID1234550639]). The abstracts were published today on the ASH (Free ASH Whitepaper) website at www.hematology.org.

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Poster Presentations

Title: IMerge: A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) That Is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment (Abstract #4248)

Session Name: 637. Myelodysplastic Syndromes—Clinical Studies: Poster III
Session Date: Monday, December 9, 2019
Session Time: 6:00 p.m. ET – 8:00 p.m. ET

As of this year, ASH (Free ASH Whitepaper) has created a new category for abstract submissions called Trials in Progress. Abstracts for this category describe innovative clinical trials that have not reached their primary endpoint to provide opportunities for early engagement and collaboration amongst investigators, translational research, clinical and industry investigators, statisticians and regulators. The Phase 3 IMerge clinical trial will be presented as a poster in this new category, and the details of the trial design are described in the abstract.

Title: Combination Treatment with Imetelstat, a Telomerase Inhibitor, and Ruxolitinib Depletes Myelofibrosis Hematopoietic Stem Cells and Progenitor Cells (Abstract #2963)

Session Name: 635. Myeloproliferative Syndromes: Basic Science: Poster II
Session Date: Sunday, December 8, 2019
Session Time: 6:00 p.m. ET – 8:00 p.m. ET

The abstract reports results from early, nonclinical experiments on the potential effect of combining imetelstat and ruxolitinib on malignant myelofibrosis (MF) cells. The experiments explored the hypothesis that the combination of imetelstat and ruxolitinib might create a treatment regimen for MF that could be more efficacious than using either drug alone in reducing myelofibrosis hematopoietic stem cells and hematopoietic progenitor cells. In the experiments, the regimen of sequential treatment of ruxolitinib followed by imetelstat resulted in greater reductions in the MF hematopoietic stem and progenitor cells, compared to when either drug was used alone or simultaneously. In addition, the sequential treatment regimen did not affect normal hematopoietic stem and progenitor cells. As stated in the abstract, these findings suggest that an additive inhibitory activity against malignant myelofibrosis hematopoietic stem and progenitor cells can be achieved using a sequential treatment regimen of ruxolitinib followed by imetelstat.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat consist of IMerge, a Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMbark, a Phase 2 trial in Intermediate-2 or High-risk myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.

Legend Biotech Announces Data Presentations at ASH 2019 for
JNJ-68284528 (JNJ-4528)/LCAR-B38M, an Investigational B-Cell Maturation Antigen (BCMA) Chimeric Antigen Receptor (CAR)-T Cell Therapy being Studied in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)

On November 6, 2019 Legend Biotech reported data from the Janssen Research & Development, LLC (Janssen) CARTITUDE-1 study (US) and the LEGEND-2 study (China) will be presented during the 61stAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual meeting in Orlando, Florida taking place December 7-10, 2019 (Press release, Legend Biotech, NOV 6, 2019, View Source [SID1234550607]).

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"The data presentations at ASH (Free ASH Whitepaper) 2019 represent two key milestones; the initial data from CARTITUDE-1 study in the US and the long term follow-up for the LEGEND-2 study in China," stated Yuan Xu, PhD, CEO of Legend Biotech. "In collaboration with Janssen, we are committed to the clinical development of LCAR-B38M/JNJ-4528 and are working diligently together to bring this investigational therapy to patients with multiple myeloma."

On Monday, December 9th during the Myeloma session titled: Therapy, excluding Transplantation: Novelty in CAR-T in RRMM, the first clinical data from the CARTITUDE-1 study will be presented. In the same session, long-term follow-up data from the previously reported LEGEND-2 study in China for the 57 patients enrolled at the Second Affiliated Hospital of Xi’an Jiaotong University will be presented, with updated data.

Additionally, updated results for the 17 patients enrolled in the LEGEND-2 study at the Shanghai Ruijin Hospital, Shanghai Changzheng Hospital, and Jiangsu Province People’s Hospital will be presented by the investigators.

Abstracts will be presented during the following dates and times:

Abstract#/Title Presenting Author Date and Time ABSTRACT #577: Results from CARTITUDE-1: a Phase 1b/2 study of JNJ-4528, a CAR-T cell therapy directed against BCMA, in patients with RRMM D Madduri Oral Presentation Monday, December 9, 7:00 am Hall D ABSTRACT #579: Long-term follow-up of a Phase 1, first-in-human open-label study of LCAR-B38M, a structurally differentiated CAR-T cell therapy targeting BCMA, in patients with RRMM BY Wang Oral Presentation Monday, December 9, 7:30 am Hall D ABSTRACT #928: Translational analysis from CARTITUDE-1, an ongoing Phase 1b/2 study of JNJ-4528 BCMA-targeted CAR-T cell therapy in RRMM, indicates preferential expansion of CD8+ T Cell central memory cell subset E Zudaire Oral Presentation Monday, December 9, 7:00 pm Valencia A (W415A) ABSTRACT #1858: Updated Phase 1 results of a first-in-human open-label study of LCAR-B38M, a structurally differentiated CAR-T cell therapy targeting BCMA LJ Chen Poster Presentation Saturday, December 7, 5:30 pm Hall B In February 2019, the US Food and Drug Administration granted Janssen an Orphan Drug Designationfor JNJ-4528. On April 3, 2019, Legend announced that the European Medicines Agency (EMA) granted Janssen a PRIME1 designationfor JNJ-4528, which was supported by results from the Phase 1b/2

CARTITUDE-1 study (NCT03548207) 2 and the Phase 1/2 LEGEND-2 study (NCT03090659)3 evaluating LCAR-B38M in RRMM. About LEGEND-2 LEGEND-2 (NCT03090659) is an ongoing single-arm, open-label Phase 1/2 study of 74 patients being conducted at four participating hospitals in China evaluating the efficacy and safety of LCAR-B38M for the treatment of relapsed or refractory multiple myeloma.

About CARTIFAN-1
In China, the Phase 2 CARTIFAN-1 (MMY2002, NCT03758417)4 confirmatory trial registered with the Center for Drug Evaluation (CTR20181007), is actively recruiting to further evaluate LCARB38M in patients with advanced relapsed or refractory multiple myeloma. About CARTITUDE-1 In the US, JNJ-4528 is currently being investigated in the Phase 1b/2 CARTITUDE-1 (MMY2001, NCT03548207) registration study for the treatment of patients with multiple myeloma who have received at least 3 prior lines of therapy or are double refractory to a PI and IMiD, received a PI, an IMiD, and anti-CD38 antibody and documented disease progression within 12 months of starting the most recent therapy. About CARTITUDE-2 In the global, multi-cohort Phase 2

CARTITUDE-2 (MMY2003, NCT04133636) 5 study, JNJ-4528 will be investigated in patients with multiple in various clinical settings. This study is being conducted to evaluate the overall minimal residual disease (MRD) negative rate of participantswho receive JNJ-4528.

About LocoMMotion
In the US and EU, a prospective observational study LocoMMotion (MMY4001, NCT04035226) 6 is being conducted to evaluate current real-world standards of care in patients with RRMM who received at least 3 prior lines of therapy including a PI, an IMiD, and anti-CD38 antibody. The abstract will be published in Blood.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells. 7 Although treatment may result in remission, unfortunately, patients will most likely relapse. 8 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy. 9,10 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory. 11 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.12 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.13

MEDx (Suzhou) and Lucence Partner to Co-Develop Cutting-Edge Cancer-Care Tests

On November 6, 2019 MEDx (Suzhou) Translational Medicine, and Singapore-based Lucence – a leading genomic medicine company reported an agreement to pursue a strategic partnership in China to co-develop cancer-care tests that would benefit patients and pharmaceutical companies (Press release, MedX Health, NOV 6, 2019, View Source [SID1234550594]).

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By melding MEDx’s industry-leading biomarker discovery, cancer molecular diagnostics, high-throughput sequencing and bioinformatics platforms; with Lucence’s proprietary technology platform that identifies PD-L1 rearrangement, as well as multiplex immunofluorescence that allows better prediction of anti-PD1/PD-L1 treatment outcomes, this partnership is poised to go from strength to strength in this sunrise industry of precision medicine.

"Immunotherapy is becoming more and more popular for drug development and personalized medicine in China. A good companion diagnosis is needed to complement immunotherapy. We believe through this strategic partnership with Lucence, we will achieve better outcomes for cancer diagnosis and treatment selection for cancer patients," said Dr. Nick Zhang, Chairman and CEO of MEDx (Suzhou) Translational Medicine.

"The complementary strengths of Lucence and MEDx to co-develop cancer-care tests in China will ensure that patients have access to non-invasive, cost-effective, faster and better diagnosis. With our steadfast focus on reducing avoidable cancer deaths, coupled with MEDx’s deep experience and wide presence in China, we are confident that this partnership will drive better cancer care in China," said Dr. Min-Han Tan, Founder and CEO of Lucence.