On July 29, 2021 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported a corporate update and financial results for the second quarter ending June 30, 2021 (Press release, PTC Therapeutics, JUL 29, 2021, View Source [SID1234585359]).

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"I am delighted to say all facets of our business made substantial progress this quarter and we anticipate having four registration-directed trials ongoing by next quarter," said Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics, Inc. "I am also proud of the execution of the global commercial team, which is driving the continued robust growth of the DMD franchise and has led us to raise our 2021 revenue guidance despite ongoing challenges from the pandemic."

Key Second Quarter and Other Corporate Updates:

The Duchenne muscular dystrophy (DMD) franchise had a total quarterly net product revenue of $102 million in the second quarter of 2021. This represents a 36% growth over the second quarter of 2020, continuing PTC’s trend of strong quarterly commercial revenues.
Translarna (ataluren) revenue growth was driven by expansion of the patient base, continued high compliance and broader access in existing geographies as well as continued geographic expansion including Russia, Central and Eastern Europe, Middle East and North Africa.
Emflaza (deflazacort) revenue growth was primarily due to new patient starts, continued high adherence and fewer discontinuations.
Evrysdi (risdiplam) received approval from the Ministry of Health Labor and Welfare in Japan in June 2021. Evrysdi is a product of a collaboration between PTC, Roche and the SMA Foundation.
Evrysdi is now approved in 54 countries.
In the U.S., more than 1800 patients are currently treated with Evrysdi, approaching 20% total market share.
Second Quarter Clinical Updates:

The registration-directed Phase 3 PTC923 phenylketonuria (PKU) trial, APHENITY, is expected to initiate in the third quarter of 2021.
PTC has multiple ongoing clinical trials, three of which are registration-directed clinical studies:
The MIT-E Phase 2/3 vatiquinone trial for mitochondrial epilepsy with data anticipated in the third quarter of 2022.
The MOVE-FA Phase 3 vatiquinone trial for Friedreich ataxia with data anticipated in 2023.
The FITE19 Phase 2/3 emvododstat trial in patients with COVID-19 is expected to be completed by year end 2021.
A Phase 1 healthy volunteer trial of the second Bio-e compound, PTC857, was recently completed and results demonstrated predictable pharmacology and no reported tolerability findings. This allows dose selection necessary to move forward to Phase 2, which we plan to initiate for amyotrophic lateral sclerosis (ALS) in the first quarter of 2022.
Results from additional cohorts are expected from the Phase 1 healthy volunteer trial of PTC518 for Huntington’s disease in the third quarter of this year. Phase 2 planning is already underway and is expected to be initiated by the end of 2021.
The Committee for Medicinal Products for Human Use (CHMP) imposed a clock stop in the aromatic L-amino acid decarboxylase deficiency (AADC-d) review process to allow for completion of its pre-approval inspections. This process is still ongoing and therefore the CHMP opinion is now expected in the fourth quarter of 2021.
For the Biologics License Application (BLA) for AADC-d, the third cannula surgery has been completed, and PTC will align with the FDA and expects to submit the BLA by the end of this year.
Second Quarter 2021 Financial Highlights:

Total revenues were $116.7 million for the second quarter of 2021, compared to total revenues of $75.2 million for the second quarter of 2020.
Total revenue includes net product revenue across the commercial portfolio of $103.1 million and royalty revenue of $13.6 million for the second quarter of 2021.
Translarna net product revenues were $52.6 million for the second quarter of 2021, compared to $38.6 million for the second quarter of 2020. These results reflect an increase in net product sales in existing markets as well as continued geographic expansion.
Emflaza net product revenues were $49.1 million for the second quarter of 2021, compared to $36.2 million for the second quarter of 2020. These results reflect new patient prescriptions, high compliance, and fewer discontinuations.
Roche reported first half of 2021 Evrysdi sales of approximately CHF 243 million, resulting in year-to-date royalty revenue of $20.2 million. Evrysdi is a product of a collaboration between PTC, Roche and the SMA Foundation.
U.S. GAAP (generally accepted accounting principles) research and development (R&D) expenses were $125.5 million for the second quarter of 2021, compared to $176.5 million for the second quarter of 2020. The decrease in research and development expenses is primarily related to one-time charges in the second quarter of 2020 of $53.6 million for our Censa merger, as well as $41.2 million for our commercial manufacturing service agreement with MassBiologics of the University of Massachusetts Medical School, or MassBio, related to dedicated manufacturing space for our lead gene therapy program, AADC deficiency. This was partially offset by increased investment in research programs and advancement of the clinical pipeline in the second quarter of 2021.
Non-GAAP R&D expenses were $112.0 million for the second quarter of 2021, excluding $13.4 million in non-cash stock-based compensation expense, compared to $168.0 million for the second quarter of 2020, excluding $8.6 million in non-cash stock-based compensation expense.
GAAP selling, general and administrative (SG&A) expenses were $68.9 million for the second quarter of 2021, compared to $53.7 million for the second quarter of 2020. The increase reflects our continued investment to support commercial activities including expanding our commercial portfolio, including an increase in rent and related expenses associated with entering into a long-term lease for our facility located in Hopewell Township.
Non-GAAP SG&A expenses were $56.6 million for the second quarter of 2021, excluding $12.3 million in non-cash stock-based compensation expense, compared to $45.3 million for the second quarter of 2020, excluding $8.3 million in non-cash stock-based compensation expense.
Change in the fair value of deferred and contingent consideration was $0.7 million for the second quarter of 2021, compared to $7.7 million for the second quarter of 2020. The change in fair value of deferred and contingent consideration is related to the fair valuation of potential future consideration to be paid to former equity holders of Agilis Biotherapeutics, Inc. (Agilis) in connection with PTC’s acquisition of Agilis, which closed in August 2018.
Net loss was $118.4 million for the second quarter of 2021, compared to net loss of $181.4 million for the second quarter of 2020.
Cash, cash equivalents and marketable securities was $947.1 million at June 30, 2021, compared to $1.1 billion at December 31, 2020.
Shares issued and outstanding as of June 30, 2021 were 70,559,330.
PTC Updates Full Year 2021 Guidance as Follows:

PTC now anticipates net product revenues for the DMD franchise for the full year 2021 to be between $370 and $390 million.
PTC continues to anticipate GAAP R&D and SG&A expense for the full year 2021 to be between $825 and $855 million.
PTC continues to anticipate Non-GAAP R&D and SG&A expense for the full year 2021 to be between $725 and $755 million, excluding estimated non-cash, stock-based compensation expense of $100 million.
Non-GAAP Financial Measures:
In this press release, the financial results and financial guidance of PTC are provided in accordance with GAAP and using certain non-GAAP financial measures. In particular, the non-GAAP financial measures exclude non-cash, stock-based compensation expense. These non-GAAP financial measures are provided as a complement to financial measures reported in GAAP because management uses these non-GAAP financial measures when assessing and identifying operational trends. In management’s opinion, these non-GAAP financial measures are useful to investors and other users of PTC’s financial statements by providing greater transparency into the historical and projected operating performance of PTC and the Company’s future outlook. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. Quantitative reconciliations of the non-GAAP financial measures to their respective closest equivalent GAAP financial measures are included in the table below.

Today’s Conference Call and Webcast Reminder:

PTC will host a conference call to discuss the second quarter of 2021 corporate updates and financial results today at 4:30 pm ET and can be access by dialing (877) 303-9216 (domestic) or (973) 935-8152 (international) five minutes prior to the start of the call and providing the passcode 7064479. A live, listen-only webcast of the conference call can be accessed on the investor relations section of the PTC website at www.ptcbio.com. A webcast replay of the call will be available approximately two hours after completion of the call and will be archived on the company’s website for 30 days following the call.

On July 29, 2021 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, reported the appointment of Chris H. Takimoto, M.D., Ph.D., F.A.C.P., to the role of Chief Medical Officer, effective today (Press release, IGM Biosciences, JUL 29, 2021, View Source [SID1234585375]). Dr. Takimoto will be responsible for global development of IGM’s clinical pipeline of proprietary IgM antibodies. He joins IGM with 30 years of experience in cancer research and development, most recently as Senior Vice President, Oncology, Gilead Sciences, Inc. Daniel S. Chen, M.D., Ph.D., will continue to assist the Company in a consulting capacity.

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"Dr. Takimoto has a proven track record of shepherding novel oncology product candidates through clinical development together with broad expertise in oncology and pharmacology gained through a distinguished industry, academic, and public service career," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "We look forward to working with him and our clinical team in continuing to advance our growing clinical pipeline of IgM antibodies. We would also like to thank Dr. Chen for the significant contributions he has made to the Company, including managing the initial dose escalation portion of our Phase 1 clinical trial of IGM-2323, our CD20 x CD3 T cell engager IgM antibody for non-Hodgkin’s lymphoma, and successfully launching our Phase 1 clinical trial of IGM-8444, our Death Receptor 5 agonist IGM antibody for solid and liquid tumors, and we sincerely wish him continued success in his career."

"As the pioneers of a groundbreaking new technology, IGM Biosciences has the potential to make a real difference for patients in therapeutic areas from oncology to infectious diseases to immunology and inflammation by harnessing the power of nature’s strongest antibodies, IgMs," said Dr. Takimoto. "IGM Biosciences has solved many of the challenges historically associated with engineering and manufacturing these complex molecules, and I look forward to participating in their clinical development and helping to demonstrate their full potential."

Prior to Gilead, Dr. Takimoto served as Chief Medical Officer, since February 2016, of Forty Seven, Inc., a biotechnology company formed out of Stanford University and acquired by Gilead Sciences in 2020. From September 2010 to January 2016, Dr. Takimoto served as Vice President of Experimental Medicine Early Development, Oncology Therapeutic Area for Janssen Research and Development, LLC. From 2008 to 2010, Dr. Takimoto served as Senior Director of Translational Medicine of Ortho Biotech Oncology Research and Development. He has over thirty years of experience in industry and academia, including academic positions at the University of Texas Health Science Center at San Antonio, the National Cancer Institute, and the Uniformed Services University of the Health Sciences. He also served as a Commissioned Officer in the U.S. Public Health Service. Dr. Takimoto received a B.S. in Chemistry from Stanford University, a Ph.D. in Pharmacology from Yale University, and an M.D. from Yale University School of Medicine.

On July 29, 2021 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that it will host a live conference call and webcast at 8:30 a.m. ET on Thursday, August 5, 2021 to report its second quarter 2021 financial results and provide a corporate update (Press release, Syros Pharmaceuticals, JUL 29, 2021, View Source [SID1234585391]).

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To access the live conference call, please dial 866-595-4538 (domestic) or 636-812-6496 (international), and refer to conference ID 4156527. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the presentation.

On July 29, 2021 Centene Corporation (NYSE: CNC) ("Centene" or the "Company") reported that it has priced its previously announced underwritten public offering of $1,800,000,000 aggregate principal amount of senior notes (Press release, Centene , JUL 29, 2021, View Source [SID1234585408]). The $1,800,000,000 offering of senior notes will include $500,000,000 aggregate principal amount of additional 2.450% senior notes due 2028 (the "Additional 2028 Notes") at a premium to yield 2.31% and $1,300,000,000 aggregate principal amount of new 2.625% senior notes due 2031 (together with the Additional 2028 Notes, the "Notes"). The Additional 2028 Notes will have the same terms as the Company’s existing 2.450% senior notes due 2028 (the "Existing 2028 Notes"), other than the issue date and the issue price. The offering is expected to close on or about August 12, 2021, subject to customary closing conditions.

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Centene intends to use the net proceeds from the offering of the Notes, together with a portion of the proceeds of certain term loans under the Company’s proposed amended and restated credit agreement and cash on hand to redeem all of its outstanding 5.375% senior notes due 2026 and all of WellCare Health Plans, Inc.’s, a Delaware corporation and a wholly-owned subsidiary of the Company, outstanding 5.375% senior notes due 2026 (together, the "Note Redemptions"), including all premiums, accrued interest and costs and expenses related to the Note Redemptions. Pending the application of the net proceeds of the offering for the foregoing purposes, net proceeds may be temporarily used for general corporate purposes. The foregoing does not constitute a notice of redemption or an obligation to issue a notice of redemption for the outstanding notes of any series.

The Notes will be senior unsecured obligations of the Company and will be equal in right of payment with all of the Company’s existing and future senior indebtedness and will be senior in right of payment to all of the Company’s existing and future subordinated debt. The Notes will not be guaranteed by any of the Company’s subsidiaries.

J.P. Morgan, Barclays, BofA Securities, Truist Securities and Wells Fargo Securities are acting as joint book-running managers for the offering of the Notes.

This offering is being made pursuant to an effective shelf registration statement and prospectus and a related preliminary prospectus supplement filed by the Company with the Securities and Exchange Commission (the "SEC"). Before you invest, you should read the prospectus and the related preliminary prospectus supplement, the registration statement and other documents that Centene has filed with the SEC for more complete information about Centene and this offering.

Copies of the prospectus supplement and related prospectuses for this offering can be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by calling +1 (866) 803-9204; from Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by email at [email protected], or by calling (888) 603-5847; from BofA Securities, Inc., NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attn: Prospectus Department or by email at [email protected]; from Truist Securities by email at [email protected]; and from Wells Fargo Securities, LLC, 550 S. Tryon Street, 5th Floor, Charlotte, North Carolina 28202, Attention: Leveraged Syndicate.

This press release is neither an offer to purchase nor a solicitation of an offer to buy any securities, including the Notes. There shall not be any sale of the securities described herein in any state or other 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 other jurisdiction.

On July 29, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported the publication of data from its Phase 1b OVATION 1 Study with GEN-1 in combination with neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Celsion, JUL 29, 2021, View Source [SID1234585425]). The study, authored by Premel H. Thaker, et al. is titled "GEN-1 in Combination with Neoadjuvant Chemotherapy for Patients with Advanced Epithelial Ovarian Cancer: A Phase I Dose-Escalation Study." The publication is available here.

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GEN-1 is a DNA-based interleukin-12 (IL-12) immunotherapy currently in Phase I/II clinical development for the localized treatment of advanced ovarian cancer (the OVATION 2 Study). GEN-1 is an immunotherapy that produces safe and durable local levels of IL-12, a pluripotent cytokine associated with the stimulation of innate and adaptive immune response against cancer. The GEN-1 nanoparticle comprises a DNA plasmid encoding IL-12 gene and a synthetic polymer facilitating plasmid delivery vector. Premal H. Thaker, M.D., M.S., Professor of Gynecologic Oncology and Director of Gynecologic Oncology Clinical Research at the Washington University School of Medicine at Washington University Medical Center in St. Louis, is the study chair for the OVATION program.

The OVATION 1 Study enrolled 18 patients with newly diagnosed stage IIIC and IV epithelial ovarian cancer in a standard 3+3 dose-escalation design testing four GEN-1 doses (36 mg/m2, 47 mg/m2, 61 mg/m2 and 79mg/m2) in combination with NACT (carboplatin-paclitaxel). There were 15 patients evaluable for safety, and 14 underwent interval debulking and were evaluable for Response Evaluation Criteria in Solid Tumors (RECIST).

As previously reported, there were no dose-limiting toxicities. As shown in the chart below, in the two highest doses of GEN-1 the objective response rate was 100% and the R0 resection rate was 88%. Newly published data show the chemotherapy response score (CRS), which is analyzed in this paper for the first time, was 50% in the two highest doses of GEN-1, compared with 28% from a major publication evaluating CRS scoring. The chemotherapy response score is a three-tier standardized scoring system for histological tumor regression into complete/near complete (CRS 3), partial (CRS 2) and no/minimal (CRS 1) response based on omental examination. Like R0 resection rates, CRS 3 response is believed to be a predictor of progression-free survival.

Clinical Responses: Tumor Response, Surgical Outcome, Pathological Response and Chemotherapy Response Score with NAC/GEN-1 escalating doses

Radiographic Response Total (n) Cohort 1
36 mg/m2 Cohort 2
47 mg/m2 Cohort 3
61 mg/m2 Cohort 4
79 mg/m2
Tumor Response

CR 2 1 0 0 1
PR 10 0 3 3 4
SD 2 2 0 0 0
Objective Response Rate 67 % 100 %
Surgical Outcome

R0 9 2 0 2 5
R1 3 1 2 0 0
R2 2 0 1 1 0
R0 Resection Rate 33 % 88 %
Pathological Response

cPR 1 1 0 0 0
Micro 8 1 2 1 4
Macro 5 1 1 2 1
cPR/Micro Rate 60 % 63 %
Chemotherapy
Response
Score

CRS 3 5 1 0 2 2
CRS 2 5 2 1 0 2
CRS 1 4 0 2 1 1
CRS 3 Rate 17 % 50 %
Commenting on the abstract, Dr. Thaker said, "My colleagues and I are very encouraged by the data generated from the OVATION 1 Study, which is informing the ongoing Phase I/II OVATION 2 Study. Importantly, the repeated durable increase in lL-12 and IFN-γ levels at the tumor site for an eight-week treatment period provides for a pharmacologic remodeling of the tumor microenvironment. These immunomodulatory effects of GEN-1 may result in an increased sensitivity of tumor microenvironment to other anticancer agents including cytotoxic drugs and immunotherapies such as checkpoint inhibitors and adaptive T cell therapies. The OVATION 2 Study of concurrent GEN-1 at a dose of 100 mg/m2 weekly for up to 17 doses administered during chemotherapy is actively recruiting."

Translational Responses: IL-12 and IFN-γ Levels, Response to Immune-Suppressive Agents; Ratio of CD8+ cells to Immune Suppressive Agents

Results from translational studies show the following:

A dose-dependent increase in immunostimulatory cytokines IL-12 and its downstream cytokine IFN-γ in ascitic fluid. The anticancer effects of these cytokines are widely recognized in human malignancies.
The proportion of myeloid dendritic cells in the peritoneal fluid trended higher (3.1-fold) accompanied by a similar 3.0-fold rise in CD8+ cells.
GEN-1 appeared to reduce four immunosuppressive signals (Foxp3, IDO1, PD-1 and PD-L1) within the tumor microenvironment, a trend not seen with NAC therapy alone.
GEN-1 also appeared to stimulate the body’s immune system through the production of CD4 and CD8 cells.
GEN-1 gene therapy was associated with an apparent increase in the cytotoxic state of T cells within the tumor microenvironment as indicated by the increases in the ratios of CD8+/CD4+ and CD8+/Treg cells. Indeed, higher CD8+/CD4+ T cell and CD8+/Treg ratios are considered prognostic for prolonged survival.
Junko Matsuzaki, Ph.D., Director of the Immune Analysis Facility at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. and a study author, said, "The results from our translational studies show the activation of a multitude of immune responses following GEN-1 + NAC treatment. The multifactorial nature of GEN-1 immune response built on a durable local production of IL-12 may be activating the innate and adaptive immune system creating a unique microenvironment potentially favorable to anti-tumor responses and also conducive to other therapeutic drugs that may be suboptimal as single agents due to the highly immunosuppressive tumor microenvironment in ovarian cancer. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation."

Nicholas Borys, M.D., Chief Medical Officer of Celsion, said, "We are delighted that our OVATION 1 Study has been published in the Journal of Clinical Cancer Research. As patients with advanced ovarian cancer have a poor prognosis, these data are particularly encouraging. We believe this publication will create additional awareness of the work we are doing to treat these patients and provide them with new hope. While we know that R0 resection scores are important to survival and that GEN-1 has exhibited impressive R0 scores, its ability to improve CRS is also compelling. Adding GEN-1 to standard neoadjuvant chemotherapy is safe, appears to be clinically active with translational data suggesting a positive impact on the tumor microenvironment."

About the Journal of Clinical Cancer Research

The Journal of Clinical Cancer Research is a publication of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). It publishes innovative clinical and translational cancer research studies that bridge the laboratory and the clinic. The Journal is especially interested in clinical trials evaluating new treatments, accompanied by research on pharmacology, and molecular alterations or biomarkers that predict response or resistance to treatment. The Journal also prioritizes laboratory and animal studies of new drugs and molecule-targeted agents with the potential to lead to clinical trials, and studies of targetable mechanisms of oncogenesis, progression of the malignant phenotype and metastatic disease.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the 5th deadliest malignancy among women in the United States. There are approximately 22,000 new cases of ovarian cancer every year and the majority (approximately 70%) are diagnosed in advanced stages III and IV. EOC is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75%, stage III and IV) after surgery and chemotherapy. Since the 5-year survival rates of patients with stages III and IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for regional approach to immune modulation.